−Removed: 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.
−Removed: 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;
−Removed: tislelizumab, an anti-PD-1 antibody immunotherapy for the treatment of various solid tumor and blood cancers;
−Removed: and pamiparib, a selective small molecule inhibitor of PARP1 and PARP2.
−Removed: 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.
−Removed: By leveraging our China commercial capabilities, we have in-licensed the rights to distribute 13 approved medicines for the China market.
+Added: We are a global oncology company discovering and developing innovative treatments that are more accessible and affordable to cancer patients worldwide.
+Added: We generated global revenue of approximately $2.5 billion in 2023, which increased by approximately $1.0 billion, while reducing our net loss by approximately $1.1 billion in comparison to 2022.
+Added: We currently have three approved medicines that were internally discovered and developed, including BRUKINSA ® (zanubrutinib), a small molecule inhibitor of Bruton’s Tyrosine Kinase (“BTK”) for the treatment of various blood cancers;
+Added: TEVIMBRA ® (tislelizumab), an anti-PD-1 antibody immunotherapy for the treatment of various solid tumor and blood cancers;
+Added: and PARTRUVIX ® (pamiparib), a selective small molecule inhibitor of PARP1 and PARP2.
+Added: We have obtained approvals to market BRUKINSA in the United States (“U.S.”), the People’s Republic of China (“China” or the “PRC”), the European Union (“EU”), the United Kingdom (“UK”), Canada, Australia, and additional international markets;
+Added: TEVIMBRA (tislelizumab) in the EU and China;
+Added: and PARTRUVIX in China.
+Added: By leveraging our strong commercial capabilities, we have in-licensed the rights to distribute an additional 14 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 Inc.
−Removed: ("Amgen") and Novartis Pharma AG ("Novartis") to develop and commercialize innovative medicines.
+Added: (“Amgen”) and Beijing Novartis Pharma Co., Ltd.
+Added: (“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.
−Removed: 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.
−Removed: This includes more than 30 pivotal or potentially registration-enabling trials across our portfolio, including our three internally discovered, approved medicines.
−Removed: We have enrolled in our clinical trials more than 18,000 subjects, of which approximately one-half have been outside of China.
−Removed: 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.
+Added: Recognizing the importance of clinical trial activities in our industry and the challenges associated with outsourcing to third-party contract research organizations (“CROs”), we have built our own 3,000+ person internal clinical team and are largely CRO-free.
+Added: We have conducted more than 130 clinical trials in-house, with over 22,000 subjects enrolled in approximately 45 regions.
+Added: This includes more than 40 pivotal or potentially registration-enabling trials across our portfolio.
+Added: We have built, and are expanding, our internal manufacturing capabilities.
+Added: We are building a commercial-stage biologics manufacturing and clinical R&D center at the Princeton West Innovation Park in Hopewell, New Jersey (the “Hopewell facility”), in addition to our existing state-of-the-art biologic and small molecule manufacturing facilities in China to support current and potential future demands of our medicines.
We also work with high quality contract manufacturing organizations (“CMOs”) to manufacture our internally developed clinical and commercial products.
−Removed: 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.
+Added: Since our inception in 2010, we have become a fully integrated global organization of over 10,000 employees worldwide, primarily in the U.S., China, and Europe.
Our Holding Company Structure
−Removed: 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.
+Added: We are a holding company incorporated in the Cayman Islands with operations primarily conducted through our subsidiaries in the U.S., China, UK, Switzerland, and Australia.
The following diagram depicts a summary of our corporate structure.
−Removed: Currently, our corporate structure contains no variable interest entities.
−Removed: 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.
+Added: Our corporate structure contains no variable interest entities.
+Added: We were founded with the vision to create an integrated biopharmaceutical company to address challenges in the pharmaceutical 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 13 years and have five strategic competitive advantages positioning us for success both near- and long-term:
−Removed: We have built one of the world's largest, most productive and cost-effective oncology research teams with more than 950 scientists.
−Removed: Their efforts have been validated by commercial approvals, clinical data, and collaborations that have secured $1.4 billion in collaboration payments to the company.
−Removed: We have successfully developed three commercially approved medicines from our internal discovery engine, including BRUKINSA and tislelizumab.
−Removed: We design each research program with a differentiated biological hypothesis or a first-in-class mechanism of action.
−Removed: Our lead medicine, BRUKINSA, has demonstrated superiority for both progression-free survival and overall response rate versus ibrutinib in relapsed or refractory CLL.
−Removed: 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.
−Removed: Our pipeline also includes many early-stage assets for targets like OX40, LAG-3, and TIM-3.
−Removed: We have invested in technology platforms, including CDAC protein degraders, bispecific antibodies, tri-specific antibodies, ADC, CAR-NK, and mRNA.
−Removed: Our research and innovation capabilities will ensure we discover high-quality and impactful medicines for patients.
−Removed: 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").
+Added: We have built a substantial global development and medical affairs team of 3,000+ people on five continents, allowing us to run clinical trials predominantly without reliance on CROs.
Clinical development accounts for over 75% of the cost and most of the time to develop a medicine.
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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.
−Removed: 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
−Removed: additional combination therapies.
+Added: We have built one of the world’s largest, most productive and cost-effective oncology research teams with 1,100+ scientists.
+Added: Their efforts have been validated by commercial approvals, clinical data, and collaborations that have secured $1.5 billion in collaboration payments to the company.
+Added: We have successfully developed three commercially approved medicines from our internal discovery engine, including BRUKINSA and TEVIMBRA.
+Added: We design each research program with a differentiated biological hypothesis or a first-in-class mechanism of action.
+Added: Our lead medicine, BRUKINSA, has demonstrated superiority for both progression-free survival and overall response rate versus ibrutinib in relapsed or refractory (“R/R”) chronic lymphocytic leukemia (“CLL”).
+Added: Our broad pipeline also includes internally developed products with the potential to be best-in-class or first-in-class, including sonrotoclax (our BCL-2 inhibitor) and BGB-16673 (a BTK-targeted CDAC) that have both demonstrated their potential with early data.
+Added: Our pipeline also includes many early-stage assets for targets including, pan-KRAS, PRMT5, CDK4, CDK2, B7H3 ADC, CEA-ADC, B7H4-ADC, MUC1 x CD16A bispecific antibody (“BsAb”), and Claudin6 x CD3 BsAb.
+Added: We have invested in technology platforms, including CDAC protein degraders, bispecific antibodies, tri-specific antibodies, ADCs, cell therapies, and mRNA.
+Added: Our research and innovation capabilities will ensure we discover high-quality and impactful medicines for patients.
+Added: We have built a strong commercial portfolio, centered around two foundational medicines, BRUKINSA and TEVIMBRA, that are primary revenue sources and 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 5,000 patients in 37 trials in 29 markets.
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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.
−Removed: 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.
−Removed: Our solid tumor franchise is led by our anti-PD-1 monoclonal antibody, tislelizumab, which is currently approved in China in ten indications.
−Removed: Tislelizumab has achieved the commercial market leader position in China in the PD-1/PDL-1 class.
−Removed: Outside of China, in conjunction with our partner Novartis, we have filed applications for approval in the U.S.
−Removed: 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.
−Removed: We have a differentiated international commercial organization of over 3,500 people to deliver medicines to patients around the globe.
−Removed: In China, the commercial team is actively driving the uptake of our internally developed and partnered medicines across solid tumors and hematology.
−Removed: 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.
−Removed: In North America, our U.S.
−Removed: team has continued to grow BRUKINSA sales as we launch new indications and expand to Canada.
−Removed: In Europe, we have built a targeted commercial team focused on medical thought leaders in blood cancer treatments.
−Removed: Altogether, BRUKINSA has been approved in over 65 markets, with additional filings pending or planned.
+Added: In December 2023, the U.S.
+Added: Food and Drug Administration (“FDA”) approved a label update for BRUKINSA to include superior progression-free survival (“PFS”) results from the Phase 3 ALPINE trial comparing BRUKINSA against IMBRUVICA in previously treated patients with R/R CLL.
+Added: We believe the differentiation of BRUKINSA has been recognized by the market and global BRUKINSA sales increased 128.5% in 2023 vs.
+Added: BRUKINSA allows us to build a strong position in heme-oncology and we plan to solidify our leadership in CLL with sonrotoclax (BCL2i) and our BTK-CDAC while amplifying our impact in other B-cell malignancies with progressive treatment strategies such as fixed duration and rational sequencing.
+Added: Our solid tumor franchise is led by our anti-PD-1 monoclonal antibody, TEVIMBRA, which is currently approved in China in twelve indications and has achieved the commercial market leader position in China in the PD-1/PDL-1 class.
+Added: Outside of China, TEVIMBRA has been approved in Europe and South Korea and we anticipate U.S.
+Added: approval on or before July 2024 for first-line ESCC.
+Added: With TEVIMBRA and the potentially best-in-class or first-in-class pipeline assets targeting pan-KRAS, PRMT5, CDK4, CDK2, B7H3 ADC, CEA-ADC, B7H4-ADC, MUC1 x CD16A BsAb, and Claudin6 x CD3 BsAb, we are well-positioned to build our solid tumor business and deliver innovative therapies and combinations to patients.
+Added: We have a differentiated global commercial organization of over 3,700 people to deliver medicines to patients around the globe, including over 500 in North America and Europe.
+Added: In North America, our team continues to grow BRUKINSA sales following the approvals in the U.S.
+Added: and Canada for CLL and small lymphocytic lymphoma (“SLL”) indications in 2023.
+Added: In China, the commercial team is marketing 17 internally developed and licensed medicines across solid tumors and hematology.
+Added: BRUKINSA and TEVIMBRA continue to strengthen market leadership positions in China in the BTKi and PD-1/PDL-1 classes, respectively.
+Added: Altogether, BRUKINSA has been approved in more than 65 markets, with additional filings pending or planned.
+Added: We reacquired the global rights of TEVIMBRA from Novartis in 2023 upon bilateral agreement.
+Added: TEVIMBRA received approval from EMA and South Korea and additional approvals and filings are pending or planned.
Our strategy is to commercialize our medicines broadly throughout the world.
−Removed: Our commercial capabilities have expanded into the Asia Pacific region through our affiliates, the Latin America region, and other emerging markets through distribution partners.
−Removed: 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.
+Added: Our commercial capabilities have expanded into the Asia Pacific, Latin America and Middle East regions through our affiliates or distribution partners.
+Added: 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 continue to 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.
−Removed: We already have substantial revenue from our cornerstone assets, which we expect to continue to grow significantly in 2023 and beyond.
−Removed: 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.
−Removed: We will continue to be thoughtful and strategic in how we deploy our capital, and we are committed to generating long-term value.
+Added: We had cash and cash equivalents of $3.2 billion as of December 31, 2023.
+Added: We already have substantial product revenue of $2.2 billion including from our cornerstone assets, which we expect to continue to grow significantly in 2024 and beyond.
+Added: We expect product revenue growth to outpace our operating expense growth, which will allow us to continue to improve our operating leverage and cash flow.
+Added: We will continue to be thoughtful and strategic in how we deploy our capital, and we are committed to generating long-term value for our shareholders.
Our Commercial and Registration Stage Products
−Removed: The following table summarizes the status of our commercial products and new products that are pending approval as of February 27, 2023:
+Added: The following table summarizes the status of our commercial products as of February 26, 2024:
PRODUCT LEAD INDICATIONS MECHANISM OF ACTION REGULATORY STATUS BEIGENE COMMERCIAL RIGHTS PARTNER
CLL/SLL, R/R MCL 1 , WM & R/R MZL 1 ;
−Removed: R/R MCL 2 , R/R CLL/SLL 2 & R/R WM 2 ;
−Removed: WM, R/R MZL, R/R CLL/SLL
+Added: R/R MCL 2 , R/R CLL/SLL, TN CLL/SLL, R/R WM & TN WM;
+Added: WM, R/R MZL, R/R CLL/SLL, R/R FL
BTK inhibitor Approved in more than 65 markets, incl.
U.S., China, EU, and other markets Global N/A
−Removed: 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
−Removed: Anti-PD-1 antibody Approved in China;
+Added: 1L squamous and non-squamous NSCLC/ 2/3 L NSCLC/ R/R classical hodgkin’s lymphoma2 / 2/3 L HCC2/ R/R PD-L1+ UC2, MSI-H or dMMR solid tumors, 2L ESCC, 1L NPC, 1L GC/GEJC, 1L ESCC, 1L HCC;
+Added: 2L ESCC Anti-PD-1 antibody Approved in China, EU 4 , and 3 other markets;
BLA accepted in U.S.
−Removed: MAA accepted in EU 4
−Removed: Outside North America, Japan, EU and six other European countries
3L BRCA-mutated ovarian cancer 2
2 unchanged sentences
Anti-RANK ligand antibody Approved in China Mainland China
−Removed: R/R Acute lymphocytic leukemia 8
−Removed: Anti-CD19 x anti-CD3 bispecific T-cell engager (BiTE) Approved in China Mainland China
+Added: R/R acute lymphocytic leukemia Anti-CD19 x anti-CD3 bispecific T-cell engager (BiTE) Approved in China Mainland China
R/R multiple myeloma 8
6 unchanged sentences
POBEVCY ® (Avastin biosimilar)
−Removed: Colorectal and lung cancers Anti-VEGF antibody Approved in China Greater China
+Added: Colorectal, lung, glioblastoma, ovarian, fallopian tube or primary peritoneal, and cervical cancers Anti-VEGF antibody Approved in China Greater China
+Added: BAITUOWEI ® (goserelin microspheres for injection)
+Added: Breast and prostate cancers Gonadotropin-releasing hormone (GnRH) agonist Approved in China Mainland China
TAFINLAR ® (dabrafenib)
+Added: NSCLC 5 , melanoma
BRAF inhibitor Approved in China China Broad Markets 7
MEKINIST ® (trametinib)
+Added: NSCLC 5 , melanoma
MEK inhibitor Approved in China China Broad Markets 7
2 unchanged sentences
AFINITOR ® (everolimus)
−Removed: Advanced renal cell carcinoma 6
+Added: Advanced renal cell carcinoma 6 , NET, SEGA & breast cancers
mTOR inhibitor Approved in China China Broad Markets 7
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The approval is applicable to all 27 EU member states, plus Iceland, Lichtenstein and Norway.
−Removed: For patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy.
−Removed: For patients with advanced or metastatic ESCC after prior systemic chemotherapy and for patients with NSCLC including:
+Added: For patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy, and as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC.
+Added: Accepted for review 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.
−Removed: TAFINLAR and MEKINIST are being investigated in combination by Novartis for NSCLC indications.
+Added: TAFINLAR, in combination with MEKINIST, is indicated for the treatment of patients with metastatic NSCLC with BRAF V600E mutation as detected by an FDA-approved test.
Following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy.
2 unchanged sentences
Full approval of any particular indication will depend on the results of required post-marketing study(ies) in China.
+Added: As part of the settlement agreement with BMS, the license and supply agreement covering REVLIMID and VIDAZA was terminated as of December 31, 2023, subject to our right to continuing selling inventory until it is sold out or December 31, 2024.
Abbreviations:
8 unchanged sentences
HCC = hepatocellular carcinoma;
−Removed: MAA = marketing aothorization application;
+Added: MAA = marketing authorization application;
MCL = mantle cell lymphoma;
2 unchanged sentences
MZL = marginal zone lymphoma;
+Added: NET= neuroendocrine tumor;
NPC = nasopharyngeal cancer;
1 unchanged sentence
R/R = relapsed / refractory;
+Added: SEGA= subpendymal giant cell astrocytoma;
SLL = small lymphocytic lymphoma;
2 unchanged sentences
WM = Waldenström’s macroglobulinemia
+Added: Please see the section of this Annual Report titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations” for revenue by product.
We commercialize the following internally developed cancer medicines:
BRUKINSA is a next-generation small molecule inhibitor of BTK designed to maximize BTK occupancy and minimize off-target binding effects.
−Removed: Zanubrutinib is an orally active inhibitor that covalently binds to BTK, resulting in irreversible inactivation of the enzyme.
−Removed: We are marketing BRUKINSA in the United States, China, Europe, the United Kingdom, Canada, Australia and other markets.
−Removed: In the United States, BRUKINSA received accelerated approval as a treatment for mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (November 2019), and has since also been approved for patients with Waldenström’s macroglobulinemia (WM) and relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
+Added: It is an orally active inhibitor that covalently binds to BTK, resulting in irreversible inactivation of the enzyme.
+Added: We are marketing BRUKINSA in the U.S., China, Europe, the UK, Canada, Australia, and other markets.
+Added: In the U.S., BRUKINSA received accelerated approval as a treatment for mantle cell lymphoma (“MCL”) in adult patients who have received at least one prior therapy (November 2019), and has since also been approved for patients with Waldenström’s macroglobulinemia (“WM”) and R/R marginal zone lymphoma (“MZL”) who have received at least one anti-CD20-based regimen.
The MCL and MZL indications were approved under accelerated approval based on overall response rate.
1 unchanged sentence
In January 2023, BRUKINSA was approved by the U.S.
−Removed: Food and Drug Administration (FDA) for the treatment of adult patients with CLL or small lymphocytic lymphoma (SLL).
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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").
−Removed: Currently, all three approved indications for BRUKINSA are included in the NRDL.
+Added: FDA for the treatment of adult patients with CLL or SLL.
+Added: In December 2023, the FDA approved a label update for BRUKINSA to include superior progression-free survival (“PFS”) results from the Phase 3 ALPINE trial comparing BRUKINSA against IMBRUVICA in previously treated patients with R/R CLL.
+Added: The FDA is currently reviewing a supplemental new drug application (“sNDA”) submission for BRUKINSA in R/R follicular lymphoma (“FL”) with a Prescription Drug User Free Act date in March 2024.
+Added: 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 R/R MZL and for the treatment of patients with CLL.
+Added: In November 2023, the EC approved BRUKINSA in combination with obinutuzumab for the treatment of adult patients with R/R FL who have received at least two prior lines of systemic therapy.
+Added: BRUKINSA is now approved to treat more patient populations in the EU than any other BTK inhibitor.
+Added: In China, BRUKINSA has received approval from the China National Medical Products Administration (“NMPA”) for treatment-naïve adults with CLL or SLL, treatment-naïve adults with WM, R/R CLL/SLL, R/R WM, and conditional approval for adult patients with MCL who have received at least one prior therapy.
+Added: Currently, all five approved indications for BRUKINSA are included in the updated National Reimbursement Drug List (“NRDL”) by the China National Healthcare Security Administration (“NHSA”).
BRUKINSA is approved across several indications in more than 65 markets as of February 2024.
4 unchanged sentences
Global revenues are projected to be more than $15 billion in 2028, according to published reports.
−Removed: 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.
−Removed: 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).
−Removed: 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.
+Added: Please see the section of this Annual Report titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations” for BRUKINSA net revenue generated in 2022 and 2023.
+Added: TEVIMBRA (tislelizumab)
+Added: TEVIMBRA 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.
+Added: Tislelizumab is approved in China in twelve indications:
+Added: • 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;
+Added: • for first-line treatment of patients with advanced squamous non-small cell lung cancer (“NSCLC”) in combination with chemotherapy;
+Added: • for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy;
+Added: • for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy;
+Added: • 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;
+Added: • for first-line treatment of patients with locally advanced or metastatic ESCC in combination with chemotherapy;
+Added: • for first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer (“NPC”);
+Added: • for first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma (“HCC”);
+Added: • for the treatment of patients with HCC who have received at least one systemic therapy;
+Added: • conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (“cHL”) who received at least two prior therapies;
+Added: • 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;
+Added: • 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.
−Removed: 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.
−Removed: 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.
−Removed: We are evaluating tislelizumab in a broad pivotal clinical program for both solid tumor and hematological indications, both globally and in China.
−Removed: We have initiated or completed 17 potentially registration-enabling clinical trials in China and globally, including 13 Phase 3 trials and four pivotal Phase 2 trials.
−Removed: In January 2021, we announced a collaboration and license agreement with Novartis to develop, manufacture and commercialize tislelizumab in the United States, Canada, Mexico, the EU, UK, Norway, Switzerland, Iceland, Liechtenstein, Russia and Japan (the "Novartis Territory").
−Removed: We retained worldwide rights to commercialize outside of the Novartis Territory and with our proprietary products in combination with tislelizumab.
−Removed: 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.
−Removed: In addition, Novartis has disclosed plans to submit additional marketing applications in its territory.
+Added: Tislelizumab was included in the NRDL in 2020 for cHL and UC, in 2021 for non-squamous NSCLC, squamous NSCLC and HCC, in 2022 for locally advanced or metastatic NSCLC, MSI-H solid tumors, locally advanced or metastatic ESCC following progression or intolerance to prior first-line chemotherapy, and first-line recurrent or metastatic NPC, and in 2023 for first-line locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma with high PD-L1 expression and first-line unresectable locally advanced, recurrent or metastatic ESCC.
+Added: In addition, three supplemental Biologics License Applications (“sBLAs”) for tislelizumab for patients with first-line extensive stage small cell lung cancer (“ES-SCLC”) and for patients with first-line locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (“GC/GEJ”) regardless of PD-L1 status and tislelizumab in combination with platinum-based doublet chemotherapy as neoadjuvant treatment for patients with NSCLC are under review by the Center for Drug Evaluation (“CDE”) of the NMPA.
+Added: In Europe, the EC has approved TEVIMBRA as monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic ESCC after prior platinum-based chemotherapy, along with additional filings.
+Added: In the U.S., we have filed a Biologics License Application (“BLA”) with the FDA for TEVIMBRA as a treatment for patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy.
+Added: Additionally, the FDA accepted for review a BLA for TEVIMBRA as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC.
+Added: We are evaluating tislelizumab in a broad pivotal clinical program for both solid tumor and hematological indications globally.
+Added: BeiGene has launched more than 17 potentially registration-enabling trials with tislelizumab, of which 11 Phase 3 randomized trials and 4 Phase 2 trials have already had positive readouts.
+Added: More than 900,000 patients have been prescribed TEVIMBRA globally to-date.
+Added: In September 2023, we announced that we had entered into an agreement with Novartis to regain worldwide rights to develop, manufacture, and commercialize TEVIMBRA.
Market Opportunity
2 unchanged sentences
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.
−Removed: Pamiparib is a selective small molecule inhibitor of poly ADP-ribose polymerase 1 (PARP1) and PARP2 enzymes.
+Added: PARTRUVIX (pamiparib)
+Added: PARTRUVIX is a selective small molecule inhibitor of poly ADP-ribose polymerase 1 (“PARP1”) and PARP2 enzymes.
Pamiparib has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models.
−Removed: Pamiparib is currently in global clinical development as a monotherapy or in combination with other agents for a variety of solid tumor malignancies.
−Removed: To date, more than 1,300 patients have been enrolled in clinical trials of pamiparib.
−Removed: In China, pamiparib received conditional approval for treatment of patients with germline BRCA (gBRCA) mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy in May 2021.
−Removed: Full approval for this indication is contingent upon results from ongoing corroborative trials confirming the clinical benefit of pamiparib in this population.
−Removed: Pamiparib was included in the 2021 NRDL in its approved indication.
−Removed: We are currently commercializing, or plan to commercialize, the following cancer medicines in China under an exclusive license from Amgen:
−Removed: XGEVA (denosumab) is an antibody-based RANK ligand (RANKL) inhibitor that was approved globally for the prevention of skeletal-related events ("SREs") in patients with bone metastases from solid tumors and in patients with multiple myeloma, and for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone (GCTB).
+Added: In China, PARTRUVIX received conditional approval for treatment of patients with germline BRCA (“gBRCA”) mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy in May 2021.
+Added: Full approval for this indication is contingent upon results from ongoing corroborative trials confirming the clinical benefit of PARTRUVIX in this population.
+Added: PARTRUVIX was included in the 2021 NRDL in its approved indication.
+Added: In-Licensed Products from Amgen
+Added: We are currently commercializing the following cancer medicines in China under an exclusive license from Amgen:
+Added: XGEVA (denosumab) is an antibody-based RANK ligand (“RANKL”) inhibitor that was approved globally for the prevention of skeletal-related events (“SREs”) in patients with bone metastases from solid tumors and in patients with multiple myeloma (“MM”), and for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone (“GCTB”).
XGEVA is approved in over 70 countries worldwide.
−Removed: In China, XGEVA received conditional approval in the GCTB indication in May 2019 and received conditional approval for the SRE indications in November 2020.
+Added: In China, XGEVA received conditional approval in the GCTB indication in May 2019 (converted to regular approval) and received conditional approval for the SRE indications in November 2020.
We began marketing XGEVA in China in July 2020.
In December 2020, we announced the inclusion of XGEVA in the NRDL for the treatment of GCTB, which was successfully renewed for inclusion in 2023.
+Added: Beginning in January 2024, the SRE indication was also included in the NRDL.
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”).
−Removed: 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.
+Added: In China, BLINCYTO received conditional approval as a treatment for adult patients with R/R ALL in December 2020 (converted to regular approval) and was conditionally approved in April 2022 for pediatric patients with R/R B-cell precursor ALL.
We began commercializing BLINCYTO in August 2021.
−Removed: KYPROLIS (carfilzomib), a proteasome inhibitor, has been approved in over 60 countries for use in patients with R/R multiple myeloma (MM).
+Added: KYPROLIS (carfilzomib), a proteasome inhibitor, has been approved in over 60 countries for use in patients with R/R 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.
KYPROLIS was included on the NRDL beginning in March 2023 for its approved indication in China.
−Removed: We commercialize the following cancer medicines in China under an exclusive license from BMS:
−Removed: REVLIMID (lenalidomide) is an oral immunomodulatory medicine that was approved in China in 2013 for the treatment of multiple myeloma (MM) in combination with dexamethasone in adult patients who have received at least one prior therapy.
+Added: In-Licensed Products from BMS
+Added: We commercialize the following cancer medicines in China under an exclusive license from BMS through 2024:
+Added: REVLIMID (lenalidomide) is an oral immunomodulatory medicine that was approved in China in 2013 for the treatment of MM in combination with dexamethasone in adult patients who have received at least one prior therapy.
In February 2018, REVLIMID received NMPA approval of a new indication for the treatment of MM in combination with dexamethasone in adult patients with previously untreated MM who are not eligible for transplant.
REVLIMID was listed on the NRDL in June 2017.
−Removed: In November 2019, we announced that REVLIMID received formal inclusion on the NRDL in China for R/R multiple myeloma.
+Added: In November 2019, we announced that REVLIMID received formal inclusion on the NRDL in China for R/R MM.
In November 2020 our sNDA for the use of REVLIMID in combination with rituximab in adult patients with previously treated follicular lymphoma was approved by the NMPA.
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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.
−Removed: On March 25, 2020, the NMPA suspended the importation, sales and use of ABRAXANE in China supplied to us by BMS, and the drug was subsequently recalled by BMS and is not currently available for sale in China.
−Removed: This suspension was based on inspection findings at BMS’s contract manufacturing facility in the United States.
−Removed: Additionally, in October 2021, BMS provided 180-days' notice to us, which we dispute, purporting to terminate our license to market ABRAXANE in China.
−Removed: We have not had any sales of ABRAXANE since the suspension and do not expect future revenue from ABRAXANE.
−Removed: 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.
+Added: On March 25, 2020, the NMPA suspended the importation, sales and use of ABRAXANE in China previously supplied to us by BMS, and the drug was subsequently recalled by BMS.
+Added: This suspension was based on inspection findings at BMS’s contract manufacturing facility in the U.S.
+Added: Following the suspension and recall of ABRAXANE, we initiated an arbitration proceeding against BMS which has since been settled.
+Added: As part of the settlement agreement, the license and supply agreement covering REVLIMID and VIDAZA was terminated as of December 31, 2023, subject to our right to continuing selling inventory until it is sold out or December 31, 2024.
For additional information, please see the section of this Annual Report titled “Legal Proceedings”.
−Removed: We are commercializing or planning to commercialize the following medicines in China under an exclusive license from EUSA Pharma:
+Added: In-Licensed Products from EUSA Pharma
+Added: We 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.
−Removed: 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).
−Removed: 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.
+Added: SYLVANT was approved in China in December 2021 for the treatment of adult patients with multicentric Castleman disease (“MCD”) who are HIV negative and HHV-8 negative, also known as iMCD.
+Added: Beginning in January 2024, Sylvant was included in the NRDL.
+Added: 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 R/R neuroblastoma with or without residual disease.
We began commercializing QARZIBA in December 2021.
+Added: In-Licensed Product from Bio-Thera
We commercialize the following product in China under an exclusive license from Bio-Thera:
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POBEVCY is a biosimilar to Avastin (bevacizumab) developed by Bio-Thera Solutions, Ltd., a commercial-stage biopharmaceutical company located in Guangzhou, China.
−Removed: In China, Avastin is approved for the treatment of patients with metastatic colorectal cancer, liver cancer and NSCLC.
+Added: In China, Avastin is approved for the treatment of patients with metastatic colorectal cancer, NSCLC, glioblastoma, ovarian, fallopian tube or primary peritoneal, and cervical cancers.
POBEVCY was approved by the NMPA in China in November 2021 and launched in late 2021 for the treatment of patients with advanced, metastatic or recurrent NSCLC, and metastatic colorectal cancer.
We have acquired the right to develop, manufacture and commercialize POBEVCY in China, including Hong Kong, Macau, and Taiwan.
−Removed: Bio-Thera submitted a marketing application to the EMA and a BLA to the FDA in November 2020.
+Added: In-Licensed Product from Luye Pharma
+Added: We commercialize the following product in China under an exclusive license from Luye Pharma:
+Added: BAITUOWEI ® (goserelin microspheres for injection)
+Added: Baituowei (Goserelin Microspheres for Injection), developed by Luye Pharma, is the world’s first and only approved microsphere formulation of Goserelin.
+Added: With its innovative microsphere formulation, Baituowei is able to ensure efficacy and safety while significantly improving patient experience.
+Added: Baituowei was approved by the NMPA in China in June 2023 for the treatment of patients with prostate cancer requiring androgen deprivation therapy and included in the NRDL in 2023, and was approved by the NMPA in China in September 2023 for treating breast cancer in premenopausal and perimenopausal women that can be treated with hormones.
Reimbursement and Market Access
Our sales are largely dependent on the availability and extent of coverage and reimbursement by third party payors.
−Removed: In many markets these third parties are government health systems and in some markets such as the United States there are also private payors such as private health insurers and health systems.
−Removed: In 2022, we commercialized our products in 60 markets.
+Added: In many markets these third parties are government health systems and in some markets such as the U.S.
+Added: there are also private payors such as private health insurers and health systems.
+Added: As of December 31, 2023, we have commercialized our products in over 65 markets.
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.
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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.
+Added: As additional indications are included in the NRDL, the price of the medicine is reduced to reflect increased patient demand as a result of NRDL inclusion.
+Added: In the 2023 NRDL, some new rules were added into contract renewal rules:
+Added: • For Category 1 chemical drugs, therapeutic biological products, as well as Category 1 and 3 traditional Chinese medicines, manufacturers could apply for re-negotiation.
+Added: The price cut may not necessarily be higher than that of simple contract renewal rules.
+Added: If re-negotiation is failed, the drug will lose NRDL listing.
+Added: • Drugs that have been included in negotiation list for more than 4 years (including 4) could have a half price cut based on the simple contract renewal rules.
+Added: • Drugs that have been included in negotiation list for more than 8 years (including 8) could be transferred to Category B.
Several of our medicines are listed on the NRDL.
−Removed: In the most recent NRDL list announced in January 2023, the following medicines were included in the NRDL, effective March 1, 2023:
−Removed: • Tislelizumab in nine of its eligible approved indications:
−Removed: – 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;
−Removed: and adult patients with locally advanced or metastatic squamous NSCLC who are negative
−Removed: 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);
−Removed: – For the treatment of adult patients with advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors:
+Added: In the latest NRDL list announced in December 2023, the following medicines and indications have been included in the NRDL, effective January 1, 2024:
+Added: • Tislelizumab in eleven of its eligible approved indications:
+Added: – In combination with fluoropyrimidine- and platinum-based chemotherapy, for the first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma with high PD-L1 expression (approved in February 2023 and included in the NRDL at the end of 2023);
+Added: – In combination with paclitaxel plus platinum-based or fluoropyrimidine- plus platinum-based chemotherapy, for the first-line treatment of patients with unresectable locally advanced, recurrent or metastatic ESCC (approved in May 2023 and included in the NRDL at the end of 2023);
+Added: – For the treatment of adult patients with locally advanced or metastatic non-squamous 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;
+Added: 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 at the beginning of 2023);
+Added: – For the treatment of adult patients with advanced unresectable or metastatic MSI-H or dMMR solid tumors:
patients with advanced colorectal cancer with disease progression after prior treatment with fluoropyrimidines, oxaliplatin and irinotecan;
−Removed: 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);
−Removed: – 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);
−Removed: – As a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (approved in June 2022 and included in the NRDL in 2023);
−Removed: – 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);
−Removed: – For the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with at least one systemic therapy (conditionally approved in June 2021 and included in the NRDL in 2021);
+Added: 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 at the beginning of 2023);
+Added: – For the treatment of patients with locally advanced or metastatic ESCC who have progressed after or are intolerant of prior first-line standard chemotherapy (approved in April 2022 and included in the NRDL at the beginning of 2023);
+Added: – As a first-line treatment for patients with recurrent or metastatic NPC (approved in June 2022 and included in the NRDL at the beginning of 2023);
+Added: – For use in combination with pemetrexed and platinum chemotherapy as a first-line treatment in patients with unresectable, locally advanced or metastatic non-squamous NSCLC, with EGFR genomic tumor aberrations negative and ALK genomic tumor negative (approved in June 2021 and included in the NRDL in 2021);
+Added: – For the treatment of patients with HCC who have been previously treated with at least one systemic therapy (conditionally approved in June 2021 and included in the NRDL in 2021);
– For use in combination with paclitaxel and carboplatin as a first-line treatment in patients with unresectable, locally advanced or metastatic squamous NSCLC (approved in January 2021 and included in the NRDL in 2021);
−Removed: – For the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy (conditionally approved in April 2020 and included in NRDL in 2020);
−Removed: – 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).
−Removed: • BRUKINSA in all three of its approved indications:
−Removed: – 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);
+Added: – For the treatment of patients with locally advanced or metastatic UC with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy (conditionally approved in April 2020 and included in the NRDL in 2020);
+Added: – For the treatment of patients with cHL who have received at least two prior therapies (conditionally approved in December 2019 and included in the NRDL in 2020).
+Added: • BRUKINSA in all five of its approved indications:
+Added: – For treatment-naïve patients with CLL or SLL (approved in April 2023 and included in the NRDL at the end of 2023);
+Added: – For treatment-naïve patients with WM (approved in April 2023 and included in the NRDL at the end of 2023);
+Added: – For the treatment of adult patients with WM who have received at least one prior therapy (conditionally approved in June 2021 and included in the NRDL in 2021;
+Added: converted to regular approval in May 2023);
– For the treatment of adult patients with MCL who have received at least one prior therapy (conditionally approved in June 2020 and included in the NRDL in 2020);
−Removed: – 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).
−Removed: • Pamiparib in its approved indication:
−Removed: – 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).
−Removed: • KYPROLIS in its approved indication as of March 1, 2023:
−Removed: – 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.
−Removed: • XGEVA was successfully renewed in NRDL as of March 2023 in its approved indication:
−Removed: – 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).
+Added: – For the treatment of adult patients with CLL/SLL who have received at least one prior therapy (conditionally approved in June 2020 and included in the NRDL in 2020;
+Added: converted to regular approval in May 2023).
+Added: • BAITUOWEI in one of its eligible approved indication:
+Added: – For the treatment of patients with prostate cancer requiring androgen deprivation therapy (approved in June 2023 and included in the NRDL at the end of 2023).
+Added: • SYLVANT in its approved indication:
+Added: – For the treatment of adult patients with MCD who are HIV negative and HHV-8 negative (approved in December 2021 and included in the NRDL at the end of 2023).
+Added: • XGEVA now listed as a Category B medicine and included all of the approved indications:
+Added: – Prevention of skeletal-related events (fracture, spinal cord compression, or the need for radiation or surgery to bone) in patients with MM and in patients with bone metastases from solid tumors (approved in November 2020 and included in the NRDL at the end of 2023);
+Added: – For the treatment of patients with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity (first included in the NRDL in 2020).
+Added: • PARTRUVIX successfully renewed its approved indication:
+Added: – For the treatment of patients with 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).
+Added: • KYPROLIS in its approved indication:
+Added: – In combination with dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received at least two lines of therapy, including proteasome inhibitor and immunomodulator.
+Added: (approved in July 2021 and included in the NRDL at the beginning of 2023).
Additionally, two of our medicines were listed in past NRDLs:
−Removed: 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.
+Added: REVLIMID was included in the 2017 NRDL negotiation list and later received formal inclusion in the 2019 Category B list, while VIDAZA was listed in the 2018 NRDL negotiation list and later received formal inclusion to the 2020 Category B list.
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.
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More than one company can win a given tender, and more guaranteed volume is awarded as more bidders win.
−Removed: The system is still evolving and, as such, the exact terms of how many bidders win and what amount of volume are won and at what price is also evolving.
+Added: The system is still evolving and, as such, the exact terms of how many bidders win and what amount of volume is won and at what price are also evolving.
It is common in China for pharmaceutical companies to employ patient assistance programs to help patients afford their innovative medicines.
−Removed: Usually these programs have been offered to patients who are self-paying.
+Added: These programs have typically 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.
1 unchanged sentence
We offer these types of patient assistance programs to our patients.
−Removed: In the United States, most health insurance coverage is provided by private insurers, often accessed via employer-sponsored plans, and the two main public insurance programs, Medicare and Medicaid.
+Added: In the U.S., most health insurance coverage is provided by private insurers, often accessed via employer-sponsored plans, and the two main public insurance programs, Medicare and Medicaid.
All three types of programs usually have some type of coverage for pharmaceutical products.
1 unchanged sentence
The structure of the pharmacy benefit can be quite different for different beneficiaries depending on the negotiations between plan sponsors and plan purchasers.
−Removed: There is no central list of covered pharmaceuticals in the United States, as there is no single payer system.
−Removed: As such, the prices paid for pharmaceuticals in the United States can vary.
−Removed: We offer patient assistance programs in the United States under our myBeiGene program.
+Added: There is no central list of covered pharmaceuticals in the U.S., as there is no single payer system.
+Added: As such, the prices paid for pharmaceuticals in the U.S.
+Added: We offer patient assistance programs in the U.S.
+Added: under our myBeiGene program.
This program seeks to enhance access to BRUKINSA by assisting with obtaining reimbursement, co-pay assistance when allowed, temporary supply of free product for insurance delays, and free product assistance for some uninsured and underinsured patients.
2 unchanged sentences
The following table summarizes the status of our internally-discovered drug candidates as of February 26, 2024:
−Removed: ASSET PROGRAM PHASE 1 PHASE 2 PHASE 3
−Removed: Zanubrutinib monotherapy R/R CLL/SLL
−Removed: + rituximab TN MCL and R/R MZL
−Removed: +/- venetoclax TN CLL/SLL
−Removed: + obinutuzumab R/R FL
−Removed: Tislelizumab monotherapy 2L advanced ESCC, 1L HCC, 2L/3L NSCLC
−Removed: Previously treated HCC, R/R cHL
−Removed: + chemotherapy 1L advanced ESCC, 1L GC/GEJC, 1L NPC
−Removed: + zanidatamab + chemotherapy 1L GEA
−Removed: + sitravatinib 2L NSCLC
−Removed: + fruquintinib Solid tumors
−Removed: Ociperlimab + tislelizumab 1L PD-L1 high NSCLC
−Removed: 2L PD-L1+ESCC, 2/3 L cervical cancer
−Removed: + tislelizumab + chemotherapy 1L NSCLC
−Removed: + tislelzumab + concurrent chemoradiotherapy LA NSCLC (PD-L!+)
−Removed: Surzebiclimab + tislelizumab +/- LBL-007 Solid tumors
−Removed: BGB-A445 + tislelizumab Solid tumors
−Removed: BGB-10188 + tislelizumab Solid tumors
−Removed: +/- zanubrutinib B-cell lymphoid malignancies
−Removed: +/- tislelizumab B-cell malignancies
−Removed: BGB-15025 + tislelizumab Solid tumors
−Removed: Pamiparib monotherapy 1L maintenance platinum-sensitive GC
−Removed: + temozolomide Solid tumors
−Removed: BGB-3245 monotherapy Solid tumors with BRAF mutations
−Removed: Lifirafenib + mirdametinib Solid tumors
−Removed: BGB-11417 monotherapy R/R MCL, R/R CLL/SLL
−Removed: +/- zanubrutinib Mature B-cell malignancies
−Removed: + azacitidine +/- posaconazole Myeloid malignancies
−Removed: + dexamethasone +/- carfilzomib R/R multiple myelome with t (11;14)
−Removed: BGB-16673 monotherapy B-cell malignancies
−Removed: BGB-23339 monotherapy Inflammation and immunology
−Removed: BGB-24714 +/- chemotherapy Solid tumors
−Removed: BGB-B167 +/- tislelizumab Solid tumors
−Removed: Abbreviations:
−Removed: cHL = classical Hodgkin lymphoma;
−Removed: CLL = chronic lymphocytic leukemia;
−Removed: ESCC = esophageal squamous-cell carcinoma;
−Removed: FL = follicular lymphoma;
−Removed: GC = gastric cancer;
−Removed: GEA = gastroesophageal adenocarcinoma;
−Removed: GEJC = gastroesophaegeal junction cancer;
−Removed: HCC = hepatocellular carcinoma;
−Removed: MCL = mantle cell lymphoma;
−Removed: MZL = marginal zone lymphoma;
−Removed: NPC = nasopharyngeal carcinoma;
−Removed: NSCLC = non-small cell lung cancer;
−Removed: R/R = relapsed/refractory;
−Removed: SCLC = small cell lung cancer;
−Removed: SLL = small lymphocytic lymphoma;
−Removed: TN = treatment treatment-naïve
The following table summarizes the status of our in-licensed drug candidates as of February 26, 2024:
Partner Molecule / Asset Indications Phase Commercial Rights
−Removed: Sotorasib Solid tumors, CRC, NSCLC Phase 3 China
−Removed: tarlatamab ^^
+Added: tarlatamab ^^
SCLC Phase 3 China
−Removed: acapatamab ^^ Prostate cancer, NSCLC Phase 1 China
−Removed: AMG 176 Hematologic malignancies Phase 1 China
−Removed: AMG 427 ^^ AML Phase 1 China
−Removed: AMG 509 Prostate cancer Phase 1 China
−Removed: AMG 199 ^^ GC/GEJC Phase 1 China
−Removed: AMG 650 Solid tumors Phase 1 China
−Removed: AMG 256 Solid tumors Phase 1 China
+Added: Xaluritamig Prostate cancer Phase 1 China
Sitravatinib † + Tislelizumab
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Sitravatinib † + Tislelizumab
−Removed: HCC, GC/GEJC Phase 2 Asia, Australia, New Zealand
−Removed: Sitravatinib † + Tislelizumab
−Removed: Solid tumors Phase 1 Asia, Australia, New Zealand
+Added: ESCC Phase 2 China
Zanidatamab + chemo + Tislelizumab GEA Phase 3 Asia, Australia, New Zealand
1 unchanged sentence
Zanidatamab BC, GC, GEA Phase 2 Asia, Australia, New Zealand
−Removed: ZW49 HER2 expressing cancers Phase 1 Asia, Australia, New Zealand
−Removed: Solid tumors Phase 1 Asia
+Added: Solid tumors Phase 1 Ex-Asia plus Japan
SEA-CD70 MDS, AML Phase 1 Asia, Australia, New Zealand
−Removed: DKN-01 + Tislelizumab + Chemo GC/GEJC Phase 2 Asia, Australia, New Zealand
−Removed: LBL-007 + Tislelizumab Advanced solid tumors Phase 2 Ex-China
−Removed: ABI-H3733 Chronic hepatitis B virus Phase 1 China
+Added: LBL-007 + Tislelizumab CRC, NSCLC, HNSCC, ESCC, Melanoma, NPC Phase 2 Ex-China
+Added: BG-C9074/DB1312 BC, EC, OC, CCA, sqNSCLC Phase 1a Global
+Added: CDK2i Breast cancer and other solid tumors Pre-clinical Global
+Added: INOVA-1, INOVA-2, cancer vaccine LNP NSCLC TAA and KRAS neoantigen, liver-specific LNP, and cancer vaccine LNP Pre-clinical Global
BiTE ® molecule;
1 unchanged sentence
† XmAb ® is a registered trademark of Xencor, Inc.
−Removed: Mirati is also conducting its own clinical studies with sitravatinib, including the Phas3 SAPPHIRE trial in non Sq NSCLC;
+Added: *Mirati was acquired by Bristol Myers Squibb in January 2024;
1 By MapKure, a JV with SpringWorks
8 unchanged sentences
HCC = hepatocellular carcinoma;
+Added: LNP= lipid nanoparticle;
MDS = myelodysplastic syndromes;
9 unchanged sentences
Zanubrutinib has demonstrated sustained 24-hour BTK occupancy in both the peripheral blood and lymph node compartments in patients.
−Removed: Zanubrutinib is the only BTK inhibitor to demonstrate superior progression-free survival versus IMBRUVICA ® (ibrutinib), an approved BTK inhibitor.
+Added: Zanubrutinib is the only BTK inhibitor to demonstrate superior progression-free survival in R/R CLL versus IMBRUVICA ® (ibrutinib), an approved BTK inhibitor.
Overview of Clinical Development Program and Regulatory Status
−Removed: 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.
+Added: We have announced BRUKINSA approvals around the world, including in the U.S., China, the EU, the UK, Canada, Australia, South Korea and Switzerland.
As of December 2023, 32 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.
−Removed: 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.
−Removed: Five of the 10 trials are Phase 3 and five are designed to be registration-enabling Phase 2 trials.
−Removed: 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.
−Removed: 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).
−Removed: Both trials are the basis for our approvals in CLL in the U.S.
−Removed: Our fourth Phase 3 trial is an ongoing Phase 3 confirmatory trial in patients with TN MCL (NCT04002297).
−Removed: 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).
−Removed: 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).
−Removed: Data from the ROSEWOOD trial were presented at the European Hematology Association (EHA) 2022, meeting its primary endpoint.
−Removed: 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.
+Added: Based on the clinical data to date, we believe that BRUKINSA has a best-in-class profile, BeiGene has initiated broad global pivotal programs in multiple indications, including 11 registration or registration-enabling clinical trials.
+Added: Six of the 11 trials are Phase 3, 3 are designed to be registration-enabling Phase 2 trials, and 2 are confirmatory trials.
+Added: • ROSEWOOD A Global Randomized Study of Zanubrutinib plus Obinutuzumab vs Obinutuzumab Monotherapy in Relapsed/ Refractory Follicular Lymphoma (FL) (NCT03332017).
+Added: • MAGNOLIA A Single-Arm Multicenter Study of Zanubrutinib subjects With Relapsed or Refractory Marginal Zone Lymphoma (MZL) (NCT03846427)
+Added: • A Phase 2, Single-Arm, Open-Label, Multicenter Study of the Bruton Tyrosine Kinase Inhibitor Zanubrutinib in subjects With CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma (NCT05068440).
+Added: • ASPEN A Global Randomized Study of Zanubrutinib vs Ibrutinib in Subjects With Waldenström’s Macroglobulinemia (WM) (NCT03053440).
+Added: • SEQUOIA A Global Randomized Study of Zanubrutinib vs Bendamustine Plus Rituximab in subjects With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL) (NCT03336333).
+Added: • ALPINE A Global Randomized Study of Zanubrutinib vs Ibrutinib in subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL) (NCT03734016).
+Added: • MANGROVE A Randomized Global Study Comparing Zanubrutinib Plus Rituximab vs.
+Added: Bendamustine Plus Rituximab in subjects With Previously Untreated Mantle Cell Lymphoma Who Are Ineligible for Stem Cell Transplantation (MCL) (NCT04002297).
+Added: • MAHOGANY Zanubrutinib Plus Obinutuzumab vs Lenalidomide plus Rituximab in Relapsed/ Refractory Follicular Lymphoma (FL) (NCT05100862).
+Added: • A Phase 2, Multicenter, Single-arm Study of Zanubrutinib in Patients With Previously Treated B-Cell Lymphoma Intolerant of Prior Treatment With Ibrutinib and/or Acalabrutinib.
+Added: • A Global Randomized Study of zanubrutinib vs tacrolimus in Primary Membranous Nephropathy (NCT05707377).
+Added: • A Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of Zanubrutinib in Patients With Active Proliferative Lupus Nephritis (NCT04643470).
+Added: In addition, Nature Medicine (December 9, 2023) published compelling combination data of an investigator-initiated multicenter Phase 2 trial (NCT04271956) investigating BRUKINSA plus our anti-PD-1 TEVIMBRA (tislelizumab) in CLL patients with Richter’s transformation (“RT”).
+Added: Extended follow-up data from ALPINE trial was presented at Annual American Society for Hematology (“ASH”) 2023.
+Added: In December 2023, we received a U.S.
+Added: Label Update which includes PFS superiority in R/R CLL (HR 0.65, p=0.0024);
+Added: sustained with extended follow-up.
+Added: Based on positive readout from ROSEWOOD study, EC has granted approval for the treatment of R/R FL.
+Added: Finally, we are also investigating zanubrutinib in several combination studies in MCL, MZL and CLL/SLL, including a Phase 3 trial in combination with sonrotoclax in front-line CLL/SLL.
+Added: We continue to examine opportunities for zanubrutinib combos with both sonrotoclax and tislelizumab.
We continue to pursue regulatory approvals for BRUKINSA globally.
−Removed: 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.
−Removed: Tislelizumab, an anti-PD-1 Antibody
+Added: Besides our recent label updates in CLL/SLL in the U.S.
+Added: (December 2023) and FL in EU (November 2023) we expect continued regulatory decisions for some of our global submissions this year, including potential additional approvals in more than 10 markets.
+Added: TEVIMBRA (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 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
−Removed: BeiGene has initiated or completed 21 potentially registration-enabling clinical trials in China and globally, including 13 Phase 3 trials and four pivotal Phase 2 trials intended to support regulatory submissions globally and in China.
+Added: BeiGene has launched more than 17 potentially registration-enabling clinical trials globally, including 13 Phase 3 randomized trials and 4 Phase 2 trials intended to support regulatory submissions globally.
Our trials in lung cancer include:
22 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).
−Removed: 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.
+Added: As of December 2023, we had enrolled over 13,000 subjects in clinical trials of tislelizumab in more than 30 countries, including 3,500+ subjects outside of China.
These studies include 11 multi-regional registrational trials that are designed for global regulatory approvals.
Data from our trials thus far suggested that tislelizumab was generally well-tolerated and exhibited anti-tumor activity in a variety of tumor types.
−Removed: Pamiparib, a PARP1 and PARP2 Inhibitor
−Removed: Pamiparib is a selective small molecule inhibitor of poly ADP-ribose polymerase 1 (PARP1) and PARP2 enzymes that is being evaluated as a potential monotherapy and in combinations for the treatment of various solid tumors.
−Removed: We believe that pamiparib has the potential to be differentiated from other PARP inhibitors because of its brain penetration, greater selectivity, strong DNA-trapping activity, and good oral bioavailability demonstrated in preclinical models.
+Added: PARTRUVIX (pamiparib), a PARP1 and PARP2 Inhibitor
+Added: Pamiparib is a selective small molecule inhibitor of PARP1 and PARP2 enzymes that is being evaluated as a potential monotherapy and in combinations for the treatment of various solid tumors.
Overview of Clinical Development Program and Regulatory Status
−Removed: In China, pamiparib received conditional approval in May 2021 for treatment of patients with germline BRCA (gBRCA) mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy.
+Added: In China, pamiparib received conditional approval in May 2021 for treatment of patients with gBRCA mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy.
Full approval for this indication is contingent upon results from ongoing corroborative trials confirming the clinical benefit of pamiparib in this population.
−Removed: 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).
+Added: In addition, our clinical development program includes a Phase 3 trial as a maintenance therapy in patients with platinum-sensitive recurrent OC (NCT03519230).
Clinical-Stage
+Added: Sonrotoclax (BGB-11417), a Small Molecule Bcl-2 Inhibitor
+Added: BGB-11417 is an investigational small molecule Bcl-2 inhibitor that is in late-stage clinical trials.
+Added: We have completed preclinical studies and have ongoing investigational new drug (“IND”) -enabling studies of BGB-11417, which demonstrate potent activity and high selectivity against the pro-apoptotic protein Bcl-2.
+Added: The molecule appears to be more potent than venetoclax and shows the potential to common venetoclax resistance mutations.
+Added: Further, it is more selective than venetoclax for Bcl-2 relative to Bcl-xL.
+Added: Designed with a shorter half-life, we believe this will lead to a more favorable tolerability profile and better handling.
+Added: Finally, we believe that it is well-positioned to be ideal backbone for combination therapies, especially with zanubrutinib and our BTK-CDAC in fixed duration treatment strategy.
+Added: The preliminary clinical data on pharmacokinetic/pharmacodynamic (“PK/PD”), efficacy and safety from more than 700 patients enrolled by December 2023 in different indications and in different combinations are consistent with the preclinical best-in-class hypothesis of a more potent and selective BCL2 inhibitor compared to venetoclax.
+Added: In TN-CLL sonrotoclax was safe and tolerable in combination with BRUKINSA;
+Added: with deep and durable responses.
+Added: Clinical data of a Phase 1 trial investigating TN-CLL/SLL, MZL (NCT04277637) and 1/ 2 trials investigating MM with t(11,14) was presented at ASH 2023.
+Added: With these encouraging results, our BCL2 inhibitor sonrotoclax (BGB-11417) program is steadily progressing at pivotal stage.
+Added: Clinical trials with registration-potential have already been initiated in R/R MCL globally (NCT05471843), R/R WM globally (NCT05952037) and R/R CLL/SLL for China only (NCT05479994).
+Added: Notably, we have just initiated the Phase 3 study of sonrotoclax + BRUKINSA vs venetoclax + obinutuzumab to support the development of sonrotoclax in the 1L CLL indication.
+Added: This study has started enrollment.
+Added: BGB-16673, a BTK-targeted CDAC
+Added: BGB-16673 is an investigational BTK‑targeting chimeric degradation activation compound (“CDAC”) active against both wild‑type and mutant BTK.
+Added: 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.
+Added: A Phase 1 open‑label, dose‑escalation, and dose‑expansion trial (NCT05006716) in adult patients with R/R B‑cell malignancies is currently enrolling.
+Added: Preliminary results are presented at ASH 2023.
+Added: We expect to initiate dose expansion in 2024.
+Added: BGB-10188, a PI3Kδ Inhibitor
+Added: 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.
+Added: BGB-21447, a Bcl-2 Inhibitor
+Added: BGB-21447 is an investigational Bcl-2 inhibitor being evaluated in a Phase 1 clinical trial ( NCT05828589 ) as monotherapy in mature B-cell malignancies.
+Added: In preclinical studies, BGB-21447 shows additional potency and selectivity, with a longer half-life than sonrotoclax.
+Added: We believe the differentiated profiles of sonrotoclax and BGB-21447 may lead to unique development options for these programs.
Ociperlimab (BGB-A1217), a TIGIT Inhibitor
Ociperlimab (BGB-A1217) is an investigational humanized IgG1-variant monoclonal antibody directed against TIGIT.
−Removed: 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.
+Added: An immune checkpoint molecule, ociperlimab is currently being investigated in a global Phase 3 trial, AdvanTIG-302 (NCT04746924), in combination with tislelizumab in NSCLC.
As of December 2023, more than 2,000 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.
−Removed: 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" .
−Removed: We have completed patient enrollment in the AdvanTIG-202 trial (NCT04693234) in patients with previously treated recurrent or metastatic cervical cancer.
−Removed: 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.
−Removed: Lifirafenib (BGB-283) and BGB-3245, Inhibitors of RAF
−Removed: Lifirafenib is an investigational novel small molecule inhibitor with RAF monomer and dimer inhibition activities.
−Removed: Lifirafenib has shown antitumor activities in preclinical models and in cancer patients with tumors harboring BRAF V600E mutations, non-V600E BRAF mutations or KRAS/NRAS mutations.
−Removed: We have been developing lifirafenib for the treatment of cancers with aberrations in the mitogen-activated protein kinase (MAPK), pathway, including BRAF gene mutations and KRAS/NRAS gene mutations where first generation BRAF inhibitors are not effective.
−Removed: We believe that lifirafenib as monotherapy or in combination with other agents may have potential for treating various malignancies such as melanoma, NSCLC, and endometrial cancer.
−Removed: BeiGene is working together with SpringWorks Therapeutics, Inc.
−Removed: (SpringWorks) in a global clinical collaboration and has initiated a Phase 1b clinical trial (NCT03905148) to evaluate the safety, tolerability, and preliminary efficacy of lifirafenib in combination with SpringWorks' investigational MEK inhibitor, mirdametinib (PD-0325901), in patients with advanced solid tumors.
−Removed: In addition to the collaboration, BeiGene and SpringWorks formed a separate company, MapKure, LLC, to develop BGB-3245, an investigational, selective next-generation RAF kinase inhibitor discovered by BeiGene scientists.
−Removed: MapKure has an ongoing Phase 1 clinical trial of BGB-3245 (NCT04249843) in patients with advanced or refractory tumors harboring specific v-RAF murine sarcoma viral oncogene homolog B (B-RAF) genetic mutations.
−Removed: Sitravatinib, a Multi-Kinase Inhibitor
−Removed: In January 2018, we entered into an exclusive license agreement with Mirati Therapeutics, Inc.
−Removed: (Mirati) for the development, manufacturing and commercialization of Mirati’s sitravatinib in Asia (excluding Japan and certain other countries), Australia and New Zealand.
−Removed: 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).
−Removed: 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.
−Removed: 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).
−Removed: We are evaluating sitravatinib in multiple clinical trials including a Phase 3 trial combined with tislelizumab in NSCLC (NCT04921358).
−Removed: BGB-11417, a Small Molecule Bcl-2 Inhibitor
−Removed: BGB-11417 is an investigational small molecule Bcl-2 inhibitor.
−Removed: We have completed preclinical and investigational new drug (IND) -enabling studies of BGB-11417, which demonstrated potent activity and high selectivity against the pro-apoptotic protein Bcl-2.
−Removed: The molecule appears to be more potent than venetoclax and shows the potential to overcome resistance to venetoclax.
−Removed: Further, it is more selective than venetoclax for Bcl-2 relative to Bcl-xL.
−Removed: Finally, we believe that it is well-positioned to be combined with BRUKINSA.
−Removed: 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.
−Removed: We initiated patient dosing in a Phase 2 study to evaluate BCL-2 inhibitor BGB-11417 in patients with relapsed or
−Removed: 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.
−Removed: BGB-A445, an OX40 Agonist Antibody
−Removed: BGB-A445 is an investigational agonistic antibody directed to the OX40 antigen.
−Removed: BGB-A445 is a non-ligand competing antibody that does not disrupt OX40 to OX40 ligand engagement.
−Removed: Preclinical experiments showed that BGB-A445 has increasing effectiveness at higher doses versus an antibody that was ligand-competing, which showed falling effectiveness at higher doses.
−Removed: 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.
−Removed: 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.
−Removed: We initiated patient dosing in a Phase 2 basket trial in melanoma, renal cell cancer and bladder cancer (NCT05661955).
−Removed: ZW25 (Zanidatamab), a bispecific HER2-targeted antibody
+Added: 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.
+Added: In July 2023, the agreement was mutually terminated and we regained the full global rights for ociperlimab.
+Added: Due to the changing treatment paradigm, we discontinued AdvanTIG 301 (NCT04866017), a Phase 3 trial of ociperlimab in combination with its anti-PD-1 antibody tislelizumab versus AstraZeneca’s Imfinzi (durvalumab) following concurrent chemoradiotherapy in patients with stage III unresectable NSCLC.
+Added: We will continue patient enrollment in AdvanTIG-302, while evaluating all available data to inform future development opportunities with ociperlimab.
+Added: Zanidatamab, a bispecific HER2-targeted antibody
Zanidatamab, a novel investigational Azymetric ™ bispecific antibody targeting HER2, is currently in late-stage clinical development with Zymeworks Inc.
4 unchanged sentences
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.
−Removed: Positive topline results from this trial were announced in 2022.
−Removed: 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.
−Removed: We completed enrollment in 2L biliary tract cancer in 2022.
+Added: Positive topline results from this trial were announced in 2022 and presented at ASCO 2023.
+Added: We are continuing the global Phase 3 clinical trial (NCT05152147) examining zanidatamab in combination with chemotherapy with and without tislelizumab in HER2-positive gastroesophageal cancer.
Surzebiclimab (BGB-A425), a TIM-3 Inhibitor
−Removed: Surzebiclimab (BGB-A425) is an investigational humanized IgG1-variant monoclonal antibody against T-cell immunoglobulin and mucin-domain containing-3 (TIM-3).
−Removed: We have an ongoing Phase 1/2 trial (NCT03744468) of surzebiclimab in combination with tislelizumab in various solid tumors.
+Added: Surzebiclimab (BGB-A425) is an investigational humanized IgG1-variant monoclonal antibody against T-cell immunoglobulin and mucin-domain containing-3.
+Added: We have an ongoing Phase 2 trial (NCT03744468) of surzebiclimab in combination with tislelizumab in NSCLC and HNSCC.
+Added: BGB-A445, an OX40 Agonist Antibody
+Added: BGB-A445 is an investigational agonistic antibody directed to the OX40 antigen.
+Added: BGB-A445 is a non-ligand competing antibody that does not disrupt OX40 to OX40 ligand engagement.
+Added: Preclinical experiments showed that BGB-A445 has increasing effectiveness at higher doses versus an antibody that was ligand-competing, which showed falling effectiveness at higher doses.
+Added: BGB-A445 has also showed in preclinical tests the potential to be combined with several agents.
+Added: BGB-A445 is being evaluated in a Phase 1 trial (NCT04215978) in patients with advanced solid tumors, a Phase 2 basket trial in melanoma, renal cell cancer and bladder cancer (NCT05661955), a Phase 2 umbrella trial in 1L NSCLC (NCT05635708), and a Phase 2 umbrella trial in 2L+ NSCLC (NCT06029127).
BGB-15025, a Small Molecule HPK1 Inhibitor
3 unchanged sentences
We initiated a Phase 1 trial (NCT04649385) of BGB-15025 alone and in combination with tislelizumab in patients with advanced solid tumors in 2021.
−Removed: This trial is being conducted in multiple countries globally.
−Removed: We expect to initiate dose-expansion for BGB-15025 in 2023.
−Removed: BGB-16673, a BTK-targeted CDAC
−Removed: BGB-16733 is an investigational BTK‑targeting chimeric degradation activation compound (CDAC) active against both wild‑type and mutant BTK.
−Removed: 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.
−Removed: 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.
−Removed: BGB-23339, a TYK2 inhibitor
−Removed: BGB-23339 is a potent, highly selective, allosteric, investigational tyrosine kinase 2 (TYK2) inhibitor discovered and being developed by BeiGene.
−Removed: TYK2 is a member of the JAK family and functions as a critical mediator in cytokine signaling pathways implicated in multiple immune-mediated disorders.
−Removed: 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.
−Removed: BGB-23339 is currently being evaluated in a Phase 1 clinical study (NCT05093270).
+Added: This trial is being conducted in multiple countries globally and has entered dose expansion.
+Added: BGB-15025 is also being tested in a 1L NSCLC umbrella study in combination with tislelizumab and other novel agents.
BGB-24714, a SMAC mimetic
−Removed: 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.
−Removed: BGB-B167, a CEA x 4-1BB bispecific
−Removed: BGB-B167 is an investigational first-in-class CEA x 4-1BB bispecific antibody.
−Removed: 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).
−Removed: BGB-10188 (PI3K inhibitor)
−Removed: 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.
+Added: BGB-24714 is an investigational Second Mitochondrial-derived Activator of Caspase (“SMAC”) mimetic currently enrolling in a Phase 1 clinical trial (NCT05381909) as monotherapy and in combination with paclitaxel, or in combination with chemoradiotherapy in advanced solid tumors.
+Added: BGB-26808, a HPK-1 Inhibitor
+Added: BGB-26808 is a second-generation HPK-1 inhibitor with a different scaffold from BGB-15025 being evaluated in a Phase 1 clinical trial ( NCT05981703 ) as monotherapy or in combination with tislelizumab in participants with advanced solid tumors.
+Added: Lifirafenib (BGB-283) and BGB-3245, Inhibitors of RAF
+Added: Lifirafenib is an investigational novel small molecule inhibitor with RAF monomer and dimer inhibition activities.
+Added: Lifirafenib has shown antitumor activities in preclinical models and in cancer patients with tumors harboring BRAF V600E mutations, non-V600E BRAF mutations or KRAS/NRAS mutations.
+Added: We have been developing lifirafenib for the treatment of cancers with aberrations in the mitogen-activated protein kinase (“MAPK”), pathway, including BRAF gene mutations and KRAS/NRAS gene mutations where first generation BRAF inhibitors are not effective.
+Added: We believe that lifirafenib as monotherapy or in combination with other agents may have potential for treating various malignancies such as melanoma, NSCLC, and endometrial cancer.
+Added: BeiGene is working together with SpringWorks Therapeutics, Inc.
+Added: (“SpringWorks”) in a global clinical collaboration and has initiated a Phase 1b clinical trial (NCT03905148) to evaluate the safety, tolerability, and preliminary efficacy of lifirafenib in combination with SpringWorks’ investigational MEK inhibitor, mirdametinib (PD-0325901), in patients with advanced solid tumors.
+Added: In addition to the collaboration, BeiGene and SpringWorks formed a separate company, MapKure, LLC, to develop BGB-3245, an investigational, selective next-generation RAF kinase inhibitor discovered by BeiGene scientists.
+Added: MapKure has an ongoing Phase 1 clinical trial of BGB-3245 (NCT04249843) in patients with advanced or refractory tumors harboring specific v-RAF murine sarcoma viral oncogene homolog B (“B-RAF”) genetic mutations.
+Added: BGB-30813, a DGKζ Inhibitor
+Added: BGB-30813 is an investigational DGKζ inhibitor being evaluated in a Phase 1 clinical trial ( NCT05904496 ) as monotherapy and in combination with tislelizumab in participants with advanced or metastatic solid tumors.
+Added: BGB-A3055, an anti-CCR8 Antibody
+Added: BGB-A3055 is an investigational anti-CCR8 antibody being evaluated in a Phase 1 clinical trial ( NCT05935098 ) as monotherapy or in combination with tislelizumab in participants with advanced or metastatic solid tumors.
+Added: BGB-43395, a CDK-4 Inhibitor
+Added: BGB-43395 is an investigational CDK4 inhibitor being evaluated in a Phase 1 clinical trial ( NCT06120283 ) as monotherapy or in combination with either fulvestrant or letrozole in participants with hormone receptor positive (“HR+”) and human epidermal growth factor 2 negative (“HER2-”) breast cancer (“BC”) and other advanced 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.
−Removed: 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.
+Added: 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 U.S., 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.
−Removed: Currently, we have over 60 pre-clinical programs and we believe the majority have best-in-class or first-in-class potential.
−Removed: We anticipate advancing multiple our preclinical drug candidates into the clinic in the next 12 months.
+Added: Currently, we have over 50 preclinical programs and we believe the majority have best-in-class or first-in-class potential.
+Added: We anticipate advancing many of our preclinical drug candidates into the clinic in the next 12 months.
We believe that we have the opportunity to combine tislelizumab with our preclinical candidates to target multiple points in the cancer immunity cycle.
7 unchanged sentences
We have manufacturing facilities for small molecule drugs and large molecule biologics in Suzhou and Guangzhou, China, respectively, to support the commercialization and potential future demand of our internally developed or in-licensed products.
+Added: We are also in the process of building a new campus for clinical R&D and biologics manufacturing in New Jersey, U.S.
Our manufacturing facility in Suzhou is over 13,000 square meters and consists of a manufacturing base for small molecule drug products with an annual production capacity of about 100 million tablets and capsules and a biologics clinical development production facility with 2 x 500 liters capacity to produce biologics candidates for clinical supply.
−Removed: The facility meets or exceeds design criteria of the United States, EU, and China regulatory requirements.
−Removed: The facility has received a manufacturing license to produce commercial volumes of BRUKINSA and pamiparib for the China market.
−Removed: As a result of our growing commercial and clinical demands, we have broken ground on a new small molecule manufacturing facility nearby in Suzhou that will have the capability to produce up to 600 million solid oral dosages annually.
+Added: The facility meets or exceeds design criteria of the U.S., EU, and China regulatory requirements.
+Added: The facility previously received a manufacturing license to produce commercial volumes of BRUKINSA and PARTRUVIX for the China market and successfully passed FDA inspection for BRUKINSA in 2023.
+Added: In 2023, as a result of our growing commercial and clinical demands, we opened our new small molecule manufacturing facility nearby in Suzhou with the capability to produce up to 1 billion solid oral dosages annually.
This approximately 50,000 square meter facility is expected to replace our current Suzhou site and support our growing pipeline of small molecule medicines and drug candidates.
−Removed: 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.
+Added: Our state-of-the-art commercial-scale manufacturing facility of large molecule biologics in Guangzhou is approximately 158,000 square meters.
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.
−Removed: 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.
−Removed: Phase 1 is currently approved for the end-to-end commercial production of tislelizumab for the China market.
−Removed: 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.
−Removed: 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.
−Removed: The property, located strategically in the Interstate 95
−Removed: 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.
+Added: Additionally, total committed capacity has been increased to 64,000 liters, with an additional expansion of 10,000 liters mechanically completed in 2023 with qualification expected by the end of 2024.
+Added: Phase 1 and 2 are currently approved for the end-to-end commercial production of tislelizumab for the China market.
+Added: We have purchased an adjacent tract of land to the south of the current site and expect opening in the first half of 2024.
+Added: The new campus will be equipped with the state-of-the-art ADC production facility and 2 x 500 liters biologics clinical capacity while reserving additional land for the next phase of expansion to support our growing pipeline of large molecule medicines and drug candidates.
+Added: With the ADC expansion, our Guangzhou manufacturing facility will have total biologics capacity of 65,000 liters.
+Added: We have almost completed construction at the U.S.
+Added: flagship manufacturing and clinical R&D facility at the 42-acre site at the Princeton West Innovation Park in Hopewell, New Jersey.
+Added: 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.
+Added: This site will have 8,000 liters of large molecule biologics manufacturing capacity and is anticipated to be operational in summer 2024.
Contract Manufacturing Organizations
2 unchanged sentences
We select our third-party suppliers carefully by considering a number of factors, including their qualifications, relevant expertise, production capacity, geographic proximity, reputation, track record, product quality, reliability in meeting delivery schedules, and business terms.
+Added: With our U.S.
+Added: manufacturing site expected to open this year and continued partnership with global manufacturers, we continue to diversify our global supply network and do not anticipate any disruption to supply on account of our established strategy to maintain sufficient safety stock of our products.
We have commercial supply and related agreements with most of our manufacturing service providers.
−Removed: 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.
−Removed: 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.
+Added: 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 and have added Catalent’s facility in Winchester, Kentucky for clinical and commercial use in the U.S.
+Added: and other countries outside of China.
+Added: We currently source the active pharmaceutical ingredient for BRUKINSA from a supplier in China and full qualification of a supplier outside of China is near completion and will be soon active.
In addition, we entered into a commercial supply agreement with Boehringer Ingelheim Biopharmaceuticals (China) Ltd.
(“Boehringer Ingelheim”) for tislelizumab, which is being manufactured at Boehringer Ingelheim’s facility in Shanghai, China.
−Removed: Additionally, our collaboration agreements with Novartis include the right for Novartis to manufacture tislelizumab and ociperlimab for its territory, to be managed by Novartis following tech transfer, and our right to conduct a specified percentage of production at our planned U.S.
−Removed: manufacturing site, subject to the terms of the agreements.
+Added: Additionally, we entered into an agreement with Novartis to regain worldwide rights to develop, manufacture, and commercialize tislelizumab.
+Added: We will continue to work with Novartis on development, regulatory and manufacturing priorities.
+Added: Novartis will manufacture tislelizumab for many markets worldwide and explore its potential in combination with their oncology assets.
For our commercial and clinical stage products in-licensed from Amgen, BMS and others, we rely on the licensors and their manufacturing facilities or their CMOs for the supply of those medicines and drug candidates.
18 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.
−Removed: 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
−Removed: pipeline products.
+Added: Additionally, pursuant to the terms of the Amgen Collaboration Agreement, we and Amgen have agreed to collaborate on the global clinical development and commercialization of a portfolio of Amgen clinical- and late-preclinical-stage oncology pipeline products.
Starting from the commencement of the Amgen Collaboration Agreement, we and Amgen will co-fund global development costs, with BeiGene contributing up to $1.25 billion worth of development services and cash over the term of the collaboration.
−Removed: 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.
+Added: We will be eligible to receive tiered mid-single digit royalties on net sales of each product globally outside of China 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.
2 unchanged sentences
The parties are subject to specified exclusivity requirements in China and the rest of the world.
−Removed: 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.
−Removed: 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;
−Removed: and (ii) cooperate in good faith to prepare a transition plan with the anticipated termination of AMG 510 from the Collaboration Agreement.
+Added: In connection with our ongoing assessment of the Amgen Collaboration Agreement cost-share contributions, we determined that our further investment in the development of AMG 510 was no longer commercially viable for BeiGene.
+Added: As a result, in February 2023, we entered into an amendment to the Amgen 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;
+Added: and (ii) cooperate in good faith to prepare a transition plan with the termination of AMG 510 from the Amgen 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
+Added: and Amgen (as amended, the “Share Purchase Agreement”), we issued to Amgen 206,635,013 ordinary shares in the form of 15,895,001 ADSs of the Company 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.
+Added: Pursuant to the Share Purchase Agreement, Amgen 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.
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.
−Removed: Under the terms of the Share Purchase Agreement, Amgen will also have specified registration rights upon expiration of the lock-up.
+Added: The lock-up has since expired and under the terms of the Share Purchase Agreement, Amgen now has specified registration rights.
Additionally, we have agreed to use reasonable best efforts to provide Amgen with an opportunity to participate in subsequent new securities offerings upon the same terms and conditions as other purchasers in the offering in an amount needed to allow Amgen to hold up to 20.6% of our shares, subject to applicable law and HKEx rules and other specified conditions.
2 unchanged sentences
2 (the “Second Amendment”) to the Share Purchase Agreement in order to account for periodic dilution from the issuance of shares by us, which agreement was restated in its entirety on September 24, 2020 (the “Restated Second Amendment”).
−Removed: Pursuant to the Restated Second Amendment, Amgen has an option (the “Direct Purchase Option”) to subscribe for additional ADSs in an amount necessary to enable it to increase (and subsequently maintain) its ownership at approximately 20.6% of our outstanding shares.
−Removed: 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%.
−Removed: The Direct Purchase Option (i) is exercisable by Amgen solely as a result of dilution arising from issuance of
−Removed: 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.
−Removed: The exercise period of the Direct Purchase Option commenced on December 1, 2020 and will terminate on the earliest of:
−Removed: (a) the date on which Amgen and its affiliates collectively own less than 20% of the outstanding share capital of the Company as a result of Amgen’s sale of shares;
−Removed: (b) at least 60-day advance written notice from either Amgen or the Company that such party wishes to terminate the Direct Purchase Option;
−Removed: or (c) December 1, 2023.
−Removed: The Direct Purchase Option has no vesting period.
+Added: Pursuant to the Restated Second Amendment, Amgen had an option (the “Direct Purchase Option”) to subscribe for additional ADSs in an amount necessary to enable it to increase (and subsequently maintain) its ownership at approximately 20.6% of our outstanding shares.
+Added: The Direct Purchase Option was exercisable on a monthly basis, but only if Amgen’s interest in our outstanding shares at the monthly reference date was less than 20.4%.
+Added: The Direct Purchase Option (i) was 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) was subject to annual approval by our independent shareholders each year during the term of the Restated Second Amendment.
+Added: The exercise period of the Direct Purchase Option commenced on December 1, 2020 and terminated on December 1, 2023.
+Added: On January 30, 2023, BeiGene, Ltd.
+Added: and Amgen entered into an Amendment No.
+Added: 3 (the “Third Amendment”) to the Share Purchase Agreement, pursuant to which Amgen elected to relinquish its right to appoint a designated director to the Company’s board of directors on account of the Company’s global growth.
+Added: The Company has retained Anthony C.
+Added: Hooper, who was Amgen’s director designee on the Company’s board of directors until Amgen relinquished its right to appoint a designated director.
+Added: Hooper was most recently re-elected by shareholders in 2022 to serve a three-year term ending 2025.
Novartis Collaboration
Collaboration and License Agreement for Tislelizumab
−Removed: 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”).
+Added: On January 11, 2021, BeiGene Switzerland 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 U.S., Canada, Mexico, member countries of the EU, UK, 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.
−Removed: Additionally, we are eligible to receive up to $1.3 billion upon the achievement of regulatory milestones, $250 million upon the achievement of sales milestones, and tiered royalties based on percentages of annual net sales of tislelizumab in the Licensed Territory ranging from the high-teens to high-twenties, with customary reductions in specified circumstances.
−Removed: Royalties are payable on a country-by-country basis from the time of the first commercial sale until the latest of the expiration of the last valid patent claim, the expiration of regulatory exclusivity, or 10 years after the first commercial sale of tislelizumab in the country of sale.
−Removed: Under the Novartis Collaboration and License Agreement, we and Novartis have agreed to jointly develop tislelizumab in the Licensed Territory, with Novartis responsible for regulatory submissions after a transition period and for commercialization upon regulatory approvals.
−Removed: In addition, both companies may conduct clinical trials to explore potential combinations of tislelizumab with other cancer treatments.
−Removed: We will be responsible for funding the ongoing clinical trials of tislelizumab, and Novartis has agreed to fund any new registrational, bridging, or post-marketing studies in the Licensed Territory.
−Removed: Subject to specified conditions, both parties have agreed to jointly fund other new clinical trials in the Licensed Territory agreed by the parties, provided that each party will be responsible for funding clinical trials evaluating tislelizumab in combination with its own- or third-party cancer treatments.
−Removed: We will initially be responsible for supplying tislelizumab to Novartis, with Novartis having the right to conduct manufacturing for its use in the Licensed Territory after successful transfer of the manufacturing process.
−Removed: In addition, we have an option to co-detail the product in the United States, Canada and Mexico, on an indication-by-indication basis, funded in part by Novartis.
−Removed: Each party retains the worldwide right to commercialize its propriety products in combination with tislelizumab.
−Removed: We retain the rights to manufacture and supply a specified percentage of commercial supply of tislelizumab from our planned U.S.
−Removed: manufacturing facility to be built in Hopewell, New Jersey, subject to the terms of the agreement.
−Removed: The Novartis Collaboration and License Agreement contains customary representations, warranties and covenants by the parties.
−Removed: Unless earlier terminated, the agreement will expire on a country-by-country basis upon expiration of the royalty term in such country and in its entirety upon the expiration of all applicable royalty terms in all countries in the Licensed Territory.
−Removed: We may terminate the agreement in its entirety upon written notice (i) if Novartis challenges the licensed BeiGene patents, or (ii) if Novartis files a biologics license application for its anti-PD-1 antibody, spartalizumab, in the Licensed Territory, and we do not elect to include spartalizumab as a licensed product under the agreement or Novartis does not divest the product candidate, in which case Novartis would pay us a specified termination fee.
−Removed: The agreement may be terminated by Novartis upon 120 days’ prior written notice if delivered before first commercial sale or 180 days’ prior written notice if delivered following first commercial sale of tislelizumab in the Licensed Territory, or by either party upon the other party’s bankruptcy or uncured material breach.
+Added: Additionally, we were eligible to receive up to $1.3 billion upon the achievement of regulatory milestones, $250 million upon the achievement of sales milestones, and tiered royalties based on percentages of annual net sales of tislelizumab in the Licensed Territory ranging from the high-teens to high-twenties, with customary reductions in specified circumstances.
+Added: Under the Novartis Collaboration and License Agreement, we and Novartis agreed to jointly develop tislelizumab in the Licensed Territory, with Novartis responsible for regulatory submissions after a transition period and for commercialization upon regulatory approvals.
+Added: In addition, both companies could conduct clinical trials to explore potential combinations of tislelizumab with other cancer treatments.
+Added: We were responsible for funding the ongoing clinical trials of tislelizumab, and Novartis agreed to fund any new registrational, bridging, or post-marketing studies in the Licensed Territory.
+Added: Subject to specified conditions, both parties agreed to jointly fund other new clinical trials in the Licensed Territory agreed by the parties, provided that each party would be responsible for funding clinical trials evaluating tislelizumab in combination with its own- or third-party cancer treatments.
+Added: In September 2023, we mutually agreed to terminate the Novartis Collaboration and License Agreement.
+Added: Pursuant to the termination agreement, we regained full, global rights to develop, manufacture and commercialize tislelizumab with no royalty payments due to Novartis.
+Added: Upon termination we have no further performance obligations under the collaboration, and all remaining deferred revenue balances were recognized in full.
+Added: Novartis may continue its ongoing clinical trials and has the ability to conduct future combination trials with tislelizumab subject to our approval.
+Added: We agreed to provide Novartis with ongoing clinical supply of tislelizumab to support its clinical trials, while Novartis agreed to provide us with transition services to enable key aspects of the tislelizumab development and commercialization plan to proceed without disruption, including manufacturing, regulatory, safety and clinical support.
Option, Collaboration and License Agreement for Ociperlimab
−Removed: On December 19, 2021, BeiGene Switzerland GmbH entered into an Option, Collaboration and License Agreement (the “Novartis Option, Collaboration and License Agreement”) with Novartis, pursuant to which we have granted Novartis an exclusive time-based option to receive an exclusive license to develop, manufacture and commercialize our investigational TIGIT inhibitor ociperlimab in the Licensed Territory.
−Removed: Under the Novartis Option, Collaboration and License Agreement, we received an upfront cash payment of $300 million from Novartis and are eligible to receive an additional payment of $600 million or $700 million upon exercise by Novartis of an exclusive time-based option prior to mid-2023 or late-2023, respectively, subject to receipt of required antitrust approval.
−Removed: Additionally, following option exercise, we are eligible to receive up to $745 million upon the achievement of regulatory approval milestones, $1.15 billion upon the achievement of sales milestones, and tiered royalties based on percentages of annual net sales of ociperlimab in the Licensed Territory ranging from the high-teens to mid-twenties, with customary reductions in specified circumstances.
−Removed: Royalties are payable on a country-by-country basis from the time of the first commercial sale until the latest of the expiration of the last valid patent claim, the expiration of regulatory exclusivity, or 10 years after the first commercial sale of ociperlimab in the country of sale.
−Removed: Under the Novartis Option, Collaboration and License Agreement, during the option period, Novartis has agreed to initiate, conduct and fund additional global clinical trials of ociperlimab in combination with tislelizumab in selected tumor types and we have agreed to expand enrollment in two ongoing trials.
−Removed: 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.
−Removed: In addition, both companies may conduct clinical trials globally to explore potential combinations of ociperlimab with other cancer treatments.
−Removed: 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.
−Removed: Following approval, we have agreed to provide 50% of the co-detailing and co-field medical efforts in the United States and have an option to co-detail up to 25% in Canada and Mexico, in each case funded in part by Novartis.
−Removed: Each party retains the worldwide right to commercialize its proprietary products in combination with ociperlimab, as is the case with tislelizumab under the parties' existing collaboration agreement.
−Removed: We retain the rights to manufacture and supply a specified percentage of commercial supply of ociperlimab from our planned U.S.
−Removed: manufacturing facility to be built in Hopewell, New Jersey, subject to the terms of the agreement.
−Removed: The Novartis Option, Collaboration and License Agreement contains customary representations, warranties and covenants by BeiGene and Novartis.
−Removed: Unless earlier terminated, the agreement will expire on a country-by-country basis upon the expiration of the royalty term in such country.
−Removed: The Novartis Option, Collaboration and License Agreement will expire in its entirety upon the expiration of all applicable royalty terms under the agreement in all countries in the Licensed Territory.
−Removed: The agreement may be terminated by Novartis upon 120 days’ prior written notice if delivered before first commercial sale or 180 days’ prior written notice if delivered following first commercial sale of ociperlimab in the Licensed Territory, or by either party upon the other party’s bankruptcy or uncured material breach.
−Removed: BeiGene may terminate the agreement in its entirety upon written notice if Novartis challenges the licensed BeiGene patents.
−Removed: Either party may terminate the agreement in its entirety effective immediately upon written notice to the other party (i) if the option terminates or expires, or (ii) in the event that the license effective date has not occurred within six months after the date of the Hart-Scott-Rodino Antitrust Improvements Act filing, subject to extension.
+Added: On December 19, 2021, we entered into an Option, Collaboration and License Agreement (the “Novartis Option, Collaboration and License Agreement”) with Novartis, pursuant to which we granted Novartis an exclusive time-based option to receive an exclusive license to develop, manufacture and commercialize our investigational TIGIT inhibitor ociperlimab in the Licensed Territory.
+Added: Under the Novartis Option, Collaboration and License Agreement, we received an upfront cash payment of $300 million from Novartis and were eligible to receive an additional payment of $600 million or $700 million upon exercise by Novartis of an exclusive time-based option prior to mid-2023 or late-2023, respectively, subject to receipt of required antitrust approval.
+Added: Additionally, following the option exercise, we were eligible to receive up to $745 million upon the achievement of regulatory approval milestones, $1.15 billion upon the achievement of sales milestones, and tiered royalties based on percentages of annual net sales of ociperlimab in the Licensed Territory ranging from the high-teens to mid-twenties, with customary reductions in specified circumstances.
+Added: Under the Novartis Option, Collaboration and License Agreement, during the option period, Novartis agreed to initiate, conduct and fund additional global clinical trials of ociperlimab in combination with tislelizumab in selected tumor types and we agreed to expand enrollment in two ongoing trials.
+Added: Additionally, following the option exercise, the companies 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.
+Added: We were initially 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.
+Added: In July 2023, we mutually agreed to terminate the Novartis Option, Collaboration and License Agreement.
+Added: Pursuant to the termination agreement, we regained full, global rights to develop, manufacture and commercialize ociperlimab.
+Added: Upon termination we have no further performance obligations under the collaboration, and all remaining deferred revenue balances were recognized in full.
Celgene License and Supply Agreement
−Removed: On July 5, 2017, we and Celgene Logistics Sàrl, now a wholly-owned subsidiary of BMS, entered into a License and Supply Agreement, which we refer to as the China License Agreement and which became effective on August 31, 2017, pursuant to which we were granted the right to exclusively distribute and promote BMS’s approved cancer therapies, REVLIMID, VIDAZA and ABRAXANE in China, excluding Hong Kong, Macau and Taiwan.
−Removed: In addition, if Celgene decides to commercialize a new oncology product through a third party in the licensed territory during the first five years of the term, we have a right of first negotiation to obtain the right to commercialize the product, subject to certain conditions.
+Added: On July 5, 2017, we and Celgene Logistics Sàrl, now a wholly-owned subsidiary of BMS, entered into a License and Supply Agreement, pursuant to which we were granted the right to exclusively distribute and promote BMS’s approved cancer therapies, REVLIMID, VIDAZA and ABRAXANE in China, excluding Hong Kong, Macau and Taiwan.
+Added: In addition, if Celgene decided to commercialize a new oncology product through a third party in the licensed territory during the first five years of the term, we had a right of first negotiation to obtain the right to commercialize the product, subject to certain conditions.
We subsequently assigned the agreement to our wholly-owned subsidiary, BeiGene Switzerland.
−Removed: On March 25, 2020, the NMPA suspended the importation, sales and use of ABRAXANE in China supplied to us by BMS, and the drug was subsequently recalled by BMS and is not currently available for sale in China.
−Removed: This suspension was based on inspection findings at BMS’s contract manufacturing facility in the United States.
+Added: On March 25, 2020, the NMPA suspended the importation, sales and use of ABRAXANE in China previously supplied to us by BMS, and the drug was subsequently recalled by BMS.
+Added: This suspension was based on inspection findings at BMS’s contract manufacturing facility in the U.S.
Additionally, in October 2021, BMS provided 180-days’ notice to us, which we dispute, purporting to terminate our license to market ABRAXANE in China.
−Removed: We have not had any sales of ABRAXANE since the suspension and do not expect future revenue from ABRAXANE.
−Removed: 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.
−Removed: For additional information, please see the section of this Annual Report titled “Legal Proceedings”.
−Removed: 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.
−Removed: BMS also has the right to terminate the agreement with respect to REVLIMID at any time upon written notice to us under certain circumstances.
−Removed: The China License Agreement contains customary representations and warranties and confidentiality and mutual indemnification provisions.
+Added: We initiated an arbitration proceeding against BMS asserting that it breached the terms and conditions of the license and supply agreement.
+Added: In August 2023, we entered into a settlement agreement which terminated the License and Supply Agreement on December 31, 2023, subject to our right to continue selling all inventory of REVLIMID and VIDAZA until sold out or December 31, 2024, whichever is earlier.
+Added: For additional information, please see the sections of this Annual Report titled “Legal Proceedings” and Footnote 17 of “Notes to the Consolidated Financial Statements”.
Intellectual Property
The proprietary nature of, and protection for, our medicines, drug candidates, and their methods of use are an important part of our strategy to develop and commercialize novel medicines, as described in more detail below.
−Removed: We have filed patent applications and obtained patents in the United States and other countries and regions, such as China and Europe, relating to our medicines and certain of our drug candidates, and are pursuing additional patent protection for them and for our other drug candidates and technologies.
−Removed: We rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection, including our manufacturing processes.
+Added: We have filed patent applications and obtained patents in the U.S.
+Added: and other countries and regions, such as China and Europe, relating to our medicines and certain of our drug candidates, and are pursuing additional patent protection for them and for our other drug candidates and technologies.
+Added: We sometimes rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection, including our manufacturing processes.
We also rely on know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen, and support our development programs.
−Removed: As of January 30, 2023, we owned 48 issued U.S.
+Added: As of February 14, 2024, we owned 63 issued U.S.
patents, 46 issued China patents, a number of pending U.S.
and China patent applications, and corresponding patents and patent applications internationally.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: The exact duration of the extension depends on the time that we spend in clinical studies as well as getting approval from the FDA.
−Removed: In China, the Amended PRC Patent Law provides a patent term extension of up to five years, similar to the United States.
−Removed: The key patents for our medicines and late-stage clinical drug candidates as of January 30, 2023, are summarized below:
+Added: The key patents for our medicines and late-stage clinical drug candidates as of February 14, 2024, are summarized below:
Molecule Territory General Subject Matter Expiration 1
1 unchanged sentence
Compound and composition 2034
−Removed: Use for the treatment of autoimmune diseases 2034
−Removed: Use for the treatment of B-cell proliferative disorder 2034
+Added: Oral dosage form 2034
+Added: Use for modulating Bruton’s tyrosine kinase activity 2034
Crystalline forms 2037
+Added: Use for the treatment of mantle cell lymphoma 2037
+Added: Use for the treatment of B-cell proliferative disorder 2037
+Added: Use for the treatment of B-cell proliferative disorder 2043
China Compound and composition 2034
−Removed: Tislelizumab U.S.
+Added: China Crystalline forms 2037
+Added: (Tislelizumab)
Antibodies 2033
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China Antibodies 2033
−Removed: China Antibodies 2033
−Removed: Pamiparib U.S.
Compound and composition 2031
3 unchanged sentences
Crystalline forms 2036
−Removed: Crystalline forms 2038
China Compound and composition 2031
3 unchanged sentences
Antibodies 2038
+Added: Sonrotoclax U.S.
+Added: Compound and composition 2039
+Added: China Compound and composition 2039
(1) The expected expiration does not include any additional term for patent term extensions.
−Removed: We currently have two in-licensed medicines in China from BMS.
−Removed: The key patents for them in China as of January 30, 2023 are summarized below:
−Removed: Product Territory General Subject Matter Expiration
−Removed: REVLIMID ® (lenalidomide)
−Removed: China Use for the treatment of multiple myeloma 2023
−Removed: China Use for the treatment of multiple myeloma 2023
−Removed: China Use for the treatment of multiple myeloma 2023
−Removed: China Use for the treatment of multiple myeloma 2023
−Removed: VIDAZA ® (azacitidine)
−Removed: China No patent N/A
Under our collaboration with Amgen, we have the right to commercialize three medicines in China.
−Removed: The key patents for them in China as of January 30, 2023 are summarized below:
+Added: The key patents for them in China as of February 14, 2024 are summarized below:
Product Territory General Subject Matter Expiration
−Removed: XGEVA ® (denosumab)
−Removed: China Antibodies 2022
BLINCYTO ® (blinatumomab)
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China Compound and Composition 2025
+Added: We have one in-licensed medicine in China from Shandong Luye Pharmaceutical Co., Ltd (“Luye”).
+Added: The key patent for it in China as of February 14, 2024 is summarized below:
+Added: Product Territory General Subject Matter Expiration
+Added: BAITUOWEI ® (goserelin microsphere)
+Added: China Formulation 2034
Although various extensions may be available, the life of a patent and the protection it affords, is limited.
−Removed: REVLIMID and VIDAZA face competition from generic medications, and we may face similar competition for our medicines and any approved drug candidates even if we successfully obtain patent protection.
+Added: We may face competition from generic medications for our medicines and any approved drug candidates even if we successfully obtain patent protection.
The scope, validity or enforceability of our or our collaborators’ patents may be challenged in court or other authorities, and we or they may not be successful in enforcing or defending those intellectual property rights and, as a result, may not be able to develop or market the relevant product exclusively, which would have a material adverse effect on any potential sales of that product.
−Removed: Additionally, in China, the NMPA may approve a generic version of a brand-name medicine that still has patent protection, such as has occurred with REVLIMID.
−Removed: Under our license agreements with BMS and Amgen, they retain the responsibility for, but are not obligated, to prosecute, defend and enforce the patents for these in-licensed products.
+Added: Additionally, in China, the NMPA may approve a generic version of a brand-name medicine that still has patent protection.
As such, any issued patents may not protect us from generic or biosimilar competition for these medicines.
+Added: Under our license agreement with Amgen, they retain the responsibility, but are not obligated, to prosecute, defend and enforce the patents for the corresponding in-licensed products.
+Added: Under our license agreement with Luye, Luye retains the responsibility, but is not obligated, to prosecute the in-licensed patents for the corresponding in-licensed product, and BeiGene retains the responsibility, but is not obligated, to defend and enforce the patents for the corresponding in-licensed product.
The term of individual patents may vary based on the countries in which they are obtained.
−Removed: In most countries in which we file, including the United States and China, the term of an issued patent is generally 20 years from the earliest claimed filing date of a non-provisional patent application in the applicable country.
−Removed: In the United States, a patent’s term may be lengthened in some cases by a patent term adjustment, which extends the term of a patent to account for administrative delays by the United States Patent and Trademark Office ("USPTO"), in excess of a patent applicant’s own delays during the prosecution process, or may be shortened if a patent is terminally disclaimed over a commonly owned patent having an earlier expiration date.
+Added: In most countries in which we file, including the U.S.
+Added: and China, the term of an issued patent is generally 20 years from the earliest claimed filing date of a non-provisional patent application in the applicable country.
+Added: In the U.S., a patent’s term may be lengthened in some cases by a patent term adjustment, which extends the term of a patent to account for administrative delays by the United States Patent and Trademark Office (“USPTO”), in excess of a patent applicant’s own delays during the prosecution process, or may be shortened if a patent is terminally disclaimed over a commonly owned patent having an earlier expiration date.
In addition, in certain instances, a patent term can be extended to recapture a portion of the term effectively lost in obtaining FDA regulatory approval.
However, the restoration period cannot be longer than five years and the total patent term including the restoration period must not exceed 14 years following FDA approval.
−Removed: In China, the Amended PRC Patent Law provides both patent term adjustment and patent term extension, similar to the United States.
+Added: In China, the Amended PRC Patent Law also provides both patent term adjustment and patent term extension.
In certain foreign jurisdictions similar extensions as compensation for regulatory delays are also available.
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Additionally, we currently own a number of registered trademarks and pending trademark applications.
−Removed: We currently have registered trademarks for BeiGene, our corporate logo and product names and logos in the United States, China, the EU and other jurisdictions, and we are seeking further trademark protection for BeiGene, our corporate logo, product names and logos, and other marks in jurisdictions where available and appropriate.
+Added: We currently have registered trademarks for BeiGene, our corporate logo and product names and logos in the U.S., China, the EU and other jurisdictions, and we are seeking further trademark protection for BeiGene, our corporate logo, product names and logos, and other marks in jurisdictions where available and appropriate.
We operate in a highly competitive environment and our marketed products face intense competition in regulated markets around the world.
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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.
−Removed: 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.
−Removed: In China, BRUKINSA competes with IMBRUVICA (ibrutinib), which received approval in 2017, and YINUOKAI ® (orelabrutinib) from Innocare, which was approved in 2020.
−Removed: Tislelizumab – A number of PD-1 or PD-L1 antibody medicines have been approved by the FDA.
−Removed: These include Merck’s KEYTRUDA ® (pembrolizumab), BMS’s OPDIVO ® (nivolumab), Roche’s TECENTRIQ ® (atezolizumab), AstraZeneca’s IMFINZI ® (durvalumab), Pfizer and Merck Sereno’s BAVENCIO ® (avelumab), Regeneron and Sanofi’s LIBTAYO ® (cemiplimab), and GSK's JEMPERLI ® (dostarlimab).
+Added: In January 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.
+Added: In China, BRUKINSA competes with IMBRUVICA (ibrutinib), which received approval in 2017, YINUOKAI ® (orelabrutinib) from Innocare, which was approved in 2020, and CALQUENCE ® (acalabrutinib), which was approved in 2023.
+Added: TEVIMBRA – A number of PD-1 or PD-L1 antibody medicines have been approved by the FDA or EMA.
+Added: These include Merck’s KEYTRUDA ® (pembrolizumab), BMS’s OPDIVO ® (nivolumab), Roche’s TECENTRIQ ® (atezolizumab), AstraZeneca’s IMFINZI ® (durvalumab), Pfizer and Merck Sereno’s BAVENCIO ® (avelumab), Regeneron and Sanofi’s LIBTAYO ® (cemiplimab), GSK’s JEMPERLI ® (dostarlimab), and Junshi’s toripalimab.
In the global setting, several PD-1 or PD-L1 antibody agents are in late-stage clinical development in addition to tislelizumab.
−Removed: In China, as of February 1, 2023, there are nine other approved PD-1 antibodies:
+Added: In China, as of December 25, 2023, there are nine 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), Gloria’s YUTUO ® (zimberelimab), Henlius’s HANSIZHUANG ® (serplulimab) and Lepu’s PUYOUHENG ® (pucotenlimab).
−Removed: There are four approved PD-L1 antibody agents:
−Removed: AstraZeneca's IMFINZI ® (durvalumab), Roche's TECENTRIQ ® (atezolizomab), CStone's ZEJIEMEI ® (sugemalimab), and Alphamab's ENWEIDA ® (envafolimab).
+Added: There are five approved PD-L1 antibody agents:
+Added: AstraZeneca’s IMFINZI ® (durvalumab), Roche’s TECENTRIQ ® (atezolizomab), CStone’s ZEJIEMEI ® (sugemalimab), Alphamab’s ENWEIDA ® (envafolimab), and Hengrui’s AIRUILI ® (adebrelimab).
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.
−Removed: Pamiparib – We are competing with multiple PARP inhibitors in China.
+Added: PARTRUVIX – We are competing with multiple PARP inhibitors in China.
AstraZeneca received approval for olaparib in August 2018.
3 unchanged sentences
To our knowledge, there are currently no approved anti-TIGIT antibodies and the most advanced agent is in Phase 3 development.
+Added: Sonrotoclax – We are aware of several pharmaceutical companies developing BCL2 inhibitors, including AbbVie, Roche, Ascentage Pharma, Fochon Pharma, Chia Tai Tianqing Pharmaceutical, AstraZeneca, Lupeng Pharmaceutical, TargetRx, Novartis, Servier, Zentalis Pharmaceuticals and InnoCare Pharma.
+Added: To our knowledge, venetoclax was approved by the FDA in April 2016, the EMA in December 2016 and by the NMPA in December 2020.
Many of the larger companies we compete with are well-capitalized and dedicate a significant number of financial resources to support their research and development, while using business development to supplement their internal pipelines.
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This requires us to devote substantial funds and resources to R&D to prevent or slow the erosion of the sales of our existing products and potential sales of products in development.
+Added: Please see the section of this Annual Report titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations” for R&D expenses incurred in 2022 and 2023.
The main forms of competition include efficacy, safety, and cost.
2 unchanged sentences
We also have and will continue to enter into co-promotion, contract sales force or other such arrangements with third parties, for example, where our own direct sales force is not large enough or sufficiently well-aligned to achieve maximum market penetration.
+Added: Furthermore, robust compliance system, science-based promotion model, and integrated management will also be competitive advantage in the industry in the long run, which we invest significant effort to establish.
Government Regulation
−Removed: 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
−Removed: developing and commercializing.
+Added: Government authorities in the U.S., 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.
1 unchanged sentence
Government Regulation and Product Approval
−Removed: In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act ("FDCA"), and its implementing regulations, and biologics under the FDCA, its implementing regulations, and the Public Health Service Act ("PHSA"), and its implementing regulations.
−Removed: Cancer therapies are sometimes characterized according to line of therapy, and the FDA often approves new therapies initially only for second or third-line use.
−Removed: When cancer is detected early enough, first line therapy may be adequate to cure the cancer or prolong life without a cure.
−Removed: Whenever first line therapy, usually chemotherapy, hormone therapy, radiation, surgery or a combination of these, proves unsuccessful, second line therapy may be administered.
−Removed: Second line therapies often consist of more chemotherapy, radiation, antibody drugs, tumor targeted small molecule drugs or a combination of these.
−Removed: Third line therapies can include bone marrow transplantation, antibody and small molecule targeted therapies, and more invasive forms of surgery.
−Removed: In some cases, new technologies and investigational medicines, as part of a clinical trial, may be used as any line of therapy.
+Added: In the U.S., the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act (“FDCA”), and its implementing regulations, and biologics under the FDCA, its implementing regulations, and the Public Health Service Act (“PHSA”), and its implementing regulations.
Drug Development Process
−Removed: The process required by the FDA before a drug or biologic may be marketed in the United States generally involves the following:
+Added: The process required by the FDA before a drug or biologic may be marketed in the U.S.
+Added: generally involves the following:
• completion of preclinical laboratory tests and animal studies according to Good Laboratory Practices (“GLP”) guidance;
14 unchanged sentences
An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or literature, to the FDA as part of the IND.
−Removed: The sponsor must also include a protocol detailing, among other things, the objectives of the initial clinical trial, dosing procedures, subject selection and exclusion criteria, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated if the initial clinical trial lends itself to an efficacy evaluation.
+Added: The sponsor must also include a protocol detailing, among other things, the objectives of the initial first-in-human clinical trial, dosing procedures, subject selection and exclusion criteria, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated if the initial clinical trial lends itself to an efficacy evaluation.
Some preclinical testing may continue even after the IND is submitted.
−Removed: 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
−Removed: clinical hold within that 30-day time period.
+Added: 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 full 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.
−Removed: The FDA may also impose clinical holds at any time before or during clinical trials due to safety concerns or noncompliance and may be imposed on all products within a certain class of products.
The FDA also can impose partial clinical holds, for example, prohibiting the initiation of clinical trials of a certain duration or for a certain dose.
+Added: The FDA may also impose full or partial clinical holds at any time before or during clinical trials due to safety concerns or noncompliance and may be imposed on all products within a certain class of products.
All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCP regulations.
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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.
−Removed: A sponsor who wishes to conduct a clinical trial outside of the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND.
+Added: A sponsor who wishes to conduct a clinical trial outside of the U.S.
+Added: may, but need not, obtain FDA authorization to conduct the clinical trial under an IND.
If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of an NDA or BLA.
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These clinical trials are intended to evaluate the overall risk/benefit relationship of the product and provide an adequate basis for product labeling.
−Removed: In March 2022, the FDA released a final guidance entitled "Expansion Cohorts:
−Removed: 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.
−Removed: Information to support the design of individual expansion cohorts are included in IND applications and assessed by the FDA.
−Removed: 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.
1 unchanged sentence
In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA or BLA.
−Removed: Failure to exhibit due diligence with regard to conducting required Phase 4 clinical trials could result in withdrawal of approval for products.
−Removed: We refer to our Phase 1 programs as dose-escalation and dose-expansion trials.
−Removed: In addition, we refer to some of our Phase 2 programs as pivotal or registrational programs, where the results may be used to support regulatory approval in specific jurisdictions without the need to conduct a Phase 3 trial.
Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and safety reports must be submitted to the FDA and the investigators for serious and unexpected suspected AEs, any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator’s brochure, or any findings from other studies or animal or in vitro testing that suggest a significant risk in humans exposed to the product.
1 unchanged sentence
The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.
−Removed: Phase 1, Phase 2, and Phase 3 studies may not be completed successfully within any specified period, or at all.
The FDA or the sponsor may suspend or terminate, or a data safety monitoring board may recommend the suspension or termination of, a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.
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However, if a company decides to make one of its investigational products available for expanded access, the FDA reviews each request for expanded access and determines if treatment may proceed.
−Removed: A sponsor of an investigational drug for a serious disease or condition is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for individual patient access to such investigational drug.
−Removed: 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.
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The sponsor of an approved NDA or BLA is also subject to an annual prescription drug product program fee.
−Removed: The FDA reviews all NDAs and BLAs submitted to ensure that they are sufficiently complete for substantive review before it accepts them for filing.
The FDA may request additional information rather than accept an NDA or BLA for filing.
−Removed: In this event, the NDA or BLA must be re-submitted with the additional information.
−Removed: The re-submitted application also is subject to review before the FDA accepts it for filing.
−Removed: Once the submission is accepted for filing, the FDA begins an in-depth substantive review.
−Removed: The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use, and a BLA to determine whether the biologic is safe, pure, and potent for its intended use.
+Added: In this event, the NDA or BLA must be re-submitted with the additional information and the re-submitted application is subject to review before the FDA accepts it for filing.
+Added: Once the submission is accepted for filing, the FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use, and a BLA to determine whether the biologic is safe, pure, and potent for its intended use.
The FDA also evaluates whether the product’s manufacturing is cGMP-compliant to assure the product’s identity, strength, quality and purity.
Before approving an NDA or BLA, the FDA typically will inspect the facility or facilities where the product is or will be manufactured.
−Removed: The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.
+Added: The FDA will not approve an application unless it determines that the manufacturing processes and facilities comply with cGMP requirements and adequate to assure consistent production of the product within required specifications.
Additionally, before approving an NDA or BLA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP and other requirements and the integrity of the clinical data submitted to the FDA.
−Removed: The approval process can be lengthy and difficult, and the FDA may refuse to approve an NDA or BLA if the applicable regulatory criteria are not satisfied or may require additional clinical data or other data and information.
+Added: The approval process can be lengthy and difficult, and the FDA may refuse to approve an NDA or BLA if the applicable regulatory criteria are not satisfied or may require additional data and information.
Even if such data and information are submitted, the FDA may ultimately decide that the NDA or BLA does not satisfy the criteria for approval.
−Removed: Data obtained from clinical trials are not always conclusive, and the FDA may interpret data differently than we interpret the same
+Added: Data obtained from clinical trials are not always conclusive, and the FDA may interpret data differently than we interpret the same data.
The FDA will issue a complete response letter if the agency decides not to approve the NDA or BLA in its present form.
−Removed: The complete response letter usually describes all of the specific deficiencies that the FDA identified in the NDA or BLA that must be satisfactorily addressed before it can be approved.
+Added: The complete response letter usually describes the specific deficiencies identified in the NDA or BLA that must be satisfactorily addressed before it can be approved.
The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical trials.
Additionally, the complete response letter may include recommended actions that the applicant might take to place the application in a condition for approval.
−Removed: If a complete response letter is issued, the applicant may either resubmit the NDA or BLA, addressing all of the deficiencies identified in the letter, or withdraw the application or request an opportunity for a hearing.
+Added: If a complete response letter is issued, the applicant may either resubmit the NDA or BLA, addressing all of the deficiencies identified in the letter, withdraw the application or request an opportunity for a hearing.
If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.
−Removed: Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling.
−Removed: 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.
+Added: Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling, require post-approval studies, including Phase 4 clinical trials, to further assess a product’s safety and effectiveness, or may require testing and surveillance programs to monitor the safety of approved products.
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.
−Removed: Regulation of Combination Products in the United States
−Removed: Certain products may be comprised of components that would normally be regulated under different types of regulatory authorities in certain jurisdictions, and in the United States by different centers at the FDA.
+Added: Regulation of Combination Products in the U.S.
+Added: Certain products may be comprised of components that would normally be regulated under different types of regulatory authorities in certain jurisdictions, and in the U.S.
+Added: by different centers at the FDA.
These products are known as combination products.
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We are developing combination products using our own drug candidates and third-party drugs.
−Removed: Regulation of Companion Diagnostics in the United States
+Added: Regulation of Companion Diagnostics in the U.S.
If safe and effective use of a therapeutic depends on an in vitro diagnostic, then the FDA generally will require approval or clearance of that diagnostic, known as a companion diagnostic, at the same time that the FDA approves the therapeutic product.
−Removed: In August 2014, the FDA issued final guidance clarifying the requirements that will apply to approval of therapeutic products and in vitro companion diagnostics.
−Removed: According to the guidance, for novel drugs, a companion diagnostic device and its corresponding therapeutic should be approved or cleared contemporaneously by the FDA for the use indicated in the therapeutic product’s labeling.
+Added: For novel drugs, a companion diagnostic device and its corresponding therapeutic should be approved or cleared contemporaneously by the FDA for the use indicated in the therapeutic product’s labeling.
Once cleared or approved, the companion diagnostic must adhere to post-marketing requirements including the requirements of FDA’s quality system regulation, medical device reporting, recalls and corrections along with product marketing requirements and limitations.
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Additionally, the fast track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.
−Removed: Zanubrutinib was granted fast track designation by the FDA for the treatment of WM and MZL.
+Added: BRUKINSA was granted fast track designation by the FDA for the treatment of WM, MZL and R/R FL.
Tislelizumab was granted fast track designation by the FDA for the treatment of 1L HCC.
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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.
−Removed: 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.
−Removed: 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.
+Added: Under the Food and Drug Omnibus Reform Act of 2022, the FDA can require, as appropriate, that post-approval confirmatory trials be underway prior to approval or within a specific time period after accelerated approval is granted.
+Added: 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.
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.
−Removed: 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.
+Added: BRUKINSA 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 R/R MZL who have received at least one anti-CD20-based regimen.
Breakthrough Designation
−Removed: Breakthrough therapy designation is intended to expedite the development and review of a breakthrough therapy.
−Removed: 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.
+Added: Breakthrough therapy designation is intended to expedite the development and review of a drug or biologic 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.
−Removed: If so designated, the FDA shall act to expedite the development and review of the product candidate’s marketing application, including by meeting with the sponsor throughout the product candidate’s development, providing timely advice to the sponsor to ensure that the development program to gather preclinical and clinical data is as efficient as practicable, involving senior managers and experienced review staff in a cross-disciplinary review, and assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor.
+Added: If so designated, the FDA shall expedite the development and review of the product candidate’s marketing application.
The designation may be rescinded if the product candidate does not continue to meet the criteria for breakthrough therapy designation.
−Removed: Zanubrutinib was granted breakthrough therapy designation by the FDA for the treatment of adult patients with MCL who have received at least one prior therapy.
+Added: BRUKINSA was granted breakthrough therapy designation by the FDA for the treatment of adult patients with MCL who have received at least one prior therapy.
Priority Review
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Priority review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.
−Removed: 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.
−Removed: Designated Platform Technology
−Removed: 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;
−Removed: (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
−Removed: technology has the potential to be incorporated in, or utilized by, more than one product without an adverse effect on quality, manufacturing, or safety;
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: Designated platform technology status does not ensure that a product will be developed more quickly or receive FDA approval.
−Removed: 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.
+Added: The NDA for BRUKINSA was granted priority review by the FDA for the treatment of adult patients with MCL who have received at least one prior therapy.
Pediatric Information
−Removed: Under the Pediatric Research Equity Act, as amended ("PREA"), certain NDAs and BLAs and certain NDA and BLA supplements must contain data that can be used to assess the safety and efficacy of the product candidate for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
−Removed: The FDA may grant deferrals for submission of pediatric data or full or partial waivers.
−Removed: The FDCA requires that a sponsor who is planning to submit a marketing application for a product candidate that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 study.
−Removed: The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information.
−Removed: The FDA and the sponsor must reach an agreement on the PSP.
−Removed: A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.
−Removed: Unless otherwise required by regulation, PREA does not apply to a drug or biologic for an indication for which orphan designation has been granted except that PREA will apply to an original NDA or BLA for a new active ingredient that is orphan-designated if the drug or biologic is a molecularly targeted cancer product intended for the treatment of an adult cancer and is directed at a molecular target that FDA determines to be substantially relevant to the growth or progression of a pediatric cancer.
+Added: Under the Pediatric Research Equity Act of 2003, all marketing applications for new active ingredients, indications, dosage forms, dosing regimens or routes of administration must contain an assessment of the safety and effectiveness of the product for the claimed indication in pediatric patients unless this requirement is waived, deferred or inapplicable.
+Added: Under the Best Pharmaceuticals for Children Act, a product may be eligible for pediatric exclusivity, which adds six months to existing exclusivity periods and patent terms.
+Added: This exclusivity may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued written request for such a study.
Post-Approval Requirements
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In addition, changes to the manufacturing process generally require prior FDA approval before being implemented and other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review and approval.
−Removed: The Drug Supply Chain Security Act ("DSCSA") was enacted in 2013 with the aim of building an electronic system to identify and trace certain prescription drugs distributed in the United States.
−Removed: The DSCSA mandates phased-in and resource-intensive obligations for pharmaceutical manufacturers, wholesale distributors, and dispensers over a 10-year period that is expected to culminate in November 2023.
−Removed: The law’s requirements include the quarantine and prompt investigation of a suspect product to determine if it is illegitimate, and notifying trading partners and FDA of any illegitimate product.
−Removed: Drug manufacturers and other parties involved in the supply chain must also meet chain of distribution requirements for product tracking and tracing, including a requirement to place a unique product identifier on prescription drug packages.
−Removed: This identifier consists of the National Drug Code, serial number, lot number and expiration date, in the form of a 2 dimensional data matrix barcode that can be read by humans and machines.
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.
−Removed: The cGMP requirements apply to all stages of the manufacturing process, including the production, processing, sterilization, packaging, labeling, storage and shipment of the
+Added: The cGMP requirements apply to all stages of the manufacturing process, including the production, processing, sterilization, packaging, labeling, storage and shipment of the product.
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.
−Removed: The FDA may withdraw a product approval or revoke a biologics license if compliance with regulatory requirements is not maintained or if problems occur after the product reaches the market.
−Removed: Later discovery of previously unknown problems with a product may result in restrictions on the product or even complete withdrawal of the product from the market.
+Added: Additionally, manufacturers and other parties involved in the drug supply chain for prescription drug products must also comply with product tracking and tracing requirements and notify the FDA of counterfeit, diverted, stolen and intentionally adulterated products or products that are otherwise unfit for distribution in the U.S.
+Added: The FDA may withdraw a product approval, revoke a biologics license or implement restrictions on such product if compliance with regulatory requirements is not maintained or if problems occur after the product reaches the market.
Further, the failure to maintain compliance with regulatory requirements may result in administrative or judicial actions, such as fines, untitled or warning letters, holds on clinical trials, product seizures, product detention or refusal to permit the import or export of products, refusal to approve pending applications or supplements, restrictions on marketing or manufacturing, injunctions or civil or criminal penalties.
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The USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.
−Removed: In the future, if available, we intend to apply for restorations of patent term for some of our currently owned patents beyond their current expiration dates, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant NDA or BLA;
+Added: In the future, if available, we intend to apply for restorations of patent term for some of our patents beyond their current expiration dates, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant NDA or BLA;
however, there can be no assurance that any such extension will be granted to us.
Data exclusivity provisions under the FDCA can also delay the submission or the approval of certain applications.
−Removed: The FDCA provides a five-year period of non-patent data exclusivity within the United States to the first applicant to gain approval of an NDA for a new chemical entity.
+Added: The FDCA provides a five-year period of non-patent data exclusivity within the U.S.
+Added: to the first applicant to gain approval of an NDA for a new chemical entity.
A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance.
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However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.
−Removed: Regulatory exclusivity in the United States can also include pediatric exclusivity and orphan drug exclusivity.
−Removed: Pediatric exclusivity, if granted, provides an additional six months of exclusivity, which runs from the end of other regulatory exclusivity or patent periods.
−Removed: 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.
+Added: Regulatory exclusivity in the U.S.
+Added: can also include pediatric exclusivity and orphan drug exclusivity.
+Added: Pediatric exclusivity, if granted, provides an additional six months of exclusivity for all formulations, dosage forms, and indications of the active moiety and, for drugs, patent terms.
+Added: This exclusivity, which runs from the end of other regulatory exclusivity and, for drugs, patent terms, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial, provided that at the time pediatric exclusivity is granted there is not less than nine months of term remaining.
Orphan drug exclusivity is described below under “Orphan Drugs.”
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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.
−Removed: 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.
+Added: 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 one that affects fewer than 200,000 individuals in the U.S.
+Added: or that affects more than 200,000 individuals in the U.S.
+Added: 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 U.S.
Orphan drug designation must be requested before submitting an NDA or BLA.
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Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
−Removed: The first NDA or BLA applicant to receive FDA approval for a particular active ingredient to treat a particular disease or condition with FDA orphan drug designation is entitled to a seven-year exclusive marketing period in the United States for that product, for that indication.
+Added: The first NDA or BLA applicant to receive FDA approval for a particular active ingredient to treat a particular disease or condition with FDA orphan drug designation is entitled to a seven-year exclusive marketing period in the U.S.
+Added: for that product, for that indication.
Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA or BLA application user fee.
2 unchanged sentences
Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.
−Removed: Zanubrutinib was granted orphan drug designation status by the FDA for the treatment of WM, CLL, MCL and MZL (3 subtypes).
+Added: BRUKINSA was granted orphan drug designation status by the FDA for the treatment of WM, CLL, FL, MCL and MZL (3 subtypes).
Tislelizumab was granted orphan drug designation status by the FDA for the treatment of ESCC, HCC and GC.
+Added: Sonrotoclax was granted orphan drug designation status by the FDA for the treatment of AML, MM, WM and MCL.
Disclosure of Clinical Trial Information
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Pharmaceutical Coverage, Pricing, and Reimbursement
−Removed: 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.
+Added: and in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability of coverage and reimbursement from third-party payors, including government authorities, managed care providers, private health insurers and other organizations.
Patients generally rely on third-party payors to reimburse all or part of the associated healthcare costs and no uniform policy of coverage and reimbursement for drug products exists among third-party payors.
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The requirements governing drug pricing vary widely from country to country.
−Removed: 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.
+Added: For example, the EU 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.
1 unchanged sentence
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.
−Removed: Historically, products launched in the European Union do not follow price structures of the United States and generally prices tend to be significantly lower.
+Added: Historically, products launched in the EU do not follow price structures of the U.S.
+Added: and generally prices tend to be significantly lower.
Healthcare Reform
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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.
−Removed: 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.
+Added: 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.
As a result, it is unclear how such efforts to challenge, repeal or replace the ACA, will impact our business.
−Removed: Other legislative changes have been proposed and adopted in the United States since the ACA was enacted.
+Added: Other legislative changes have been proposed and adopted in the U.S.
+Added: since the ACA was enacted.
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 2031 unless additional Congressional action is taken.
−Removed: 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.
+Added: Due to the Statutory Pay-As-You-Go Act of 2010, estimated budget deficit increases resulting from the American Rescue Plan Act of 2021, and subsequent legislation, Medicare payments to providers will be further reduced starting in 2025 absent further legislation.
+Added: In 2022, the Inflation Reduction Act of 2022 (“IRA”) was enacted containing provisions that reduce the out-of-pocket spending cap for Medicare Part D beneficiaries from $7,050 to $2,000 starting in 2025, thereby effectively eliminating the coverage gap;
+Added: impose new manufacturer financial liability on certain drugs under Medicare Part D;
+Added: allow the U.S.
+Added: government to negotiate Medicare Part B and Part D price caps for certain high-cost drugs and biologics without generic or biosimilar competition;
+Added: require companies to pay rebates to Medicare for certain drug prices that increase faster than inflation;
+Added: and delay until January 1, 2032 the implementation of the U.S.
+Added: Department of Health and Human Services (“HHS”) rebate rule that would have limited the fees that pharmacy benefit managers can charge.
+Added: Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition.
+Added: The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.
+Added: The effects of the IRA on our business and the healthcare industry in general is not yet known.
+Added: In addition, President Biden has issued multiple executive orders seeking to reduce prescription drug costs.
+Added: In February 2023, HHS issued a proposal in response to an executive order from President Biden that includes a proposed prescription drug pricing model that will test whether targeted Medicare payment adjustments will sufficiently incentivize manufacturers to complete confirmatory trials for drugs approved through the FDA’s accelerated approval pathway.
+Added: Although a number of these proposed measures may require additional legislation to become effective, both the Biden administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.
+Added: Legislative and regulatory proposals have also been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products.
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.
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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.
−Removed: 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.
−Removed: 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.
−Removed: Further, authorities in Canada have passed rules designed to safeguard the Canadian drug supply from shortages.
−Removed: If implemented, importation of drugs from Canada may adversely affect the price we receive for our medicines.
−Removed: In November 2020, the U.S.
−Removed: 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.
+Added: The HHS implemented 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.
−Removed: 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.
−Removed: 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.
+Added: Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation until January 1, 2032.
+Added: 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.
+Added: In addition, there have been several changes to the 340B drug pricing program, which imposes ceilings on prices that drug manufacturers can charge for medications sold to certain health care facilities.
+Added: In 2023, the U.S.
+Added: District Court of South Carolina issued an opinion in Genesis Healthcare Inc.
+Added: Becerra et al.
+Added: that may lead to an expansion of the scope of patients eligible to access prescriptions at 340B pricing.
+Added: The outcome of this judicial proceeding is currently uncertain.
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.
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In addition, we may be subject to patient privacy regulation by both the federal government and the states in which we conduct our business prior to and after receiving regulatory approval of our product candidates.
−Removed: The laws that may affect our ability to operate include:
+Added: Some of the laws that may affect our ability to operate are detailed below:
• The federal healthcare Anti-Kickback Statute (“AKS”), which prohibits, among other things, knowingly and willfully soliciting, receiving, providing, offering or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation or arrangement of any good, facility, item or service for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs.
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Violations of the AKS carry potentially significant civil fines and criminal penalties, including imprisonment, fines, administrative federal civil monetary penalties, and exclusion from participation in federal healthcare programs.
−Removed: 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.
−Removed: There are safe harbor protections under the AKS for certain coordinated care and value-based arrangements among clinicians, providers, and others.
+Added: This law applies to our marketing practices, educational programs, pricing policies and relationships with healthcare providers.
We continue to evaluate what effect, if any, these rules will have on our business.
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The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery.
−Removed: 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.
−Removed: 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
−Removed: 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;
+Added: When an entity is determined to have violated the 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.
+Added: 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.
−Removed: Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty of violating HIPAA without actual knowledge of the statute or specific intent to violate it;
−Removed: • HIPAA, as further amended by the Health Information Technology for Economic and Clinical Health Act of 2009 ("HITECH"), and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, which impose certain requirements on certain covered healthcare providers, health plans and healthcare clearinghouses as well as their respective business associates who perform services for them that involve the creation, maintenance, receipt, use, or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information.
−Removed: HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs.
−Removed: In addition, there may be additional federal, state and non-U.S.
−Removed: 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;
−Removed: • 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.
+Added: Similar to the federal AKS, a person or entity can be found guilty of violating HIPAA without actual knowledge of the statute or specific intent to violate it.
+Added: • As further amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), HIPPA and their respective implementing regulations impose requirements on certain covered healthcare providers, health plans and healthcare clearinghouses as well as their respective business associates who perform services for them that involve the creation, maintenance, receipt, use, or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information.
+Added: HITECH also created new tiers of civil monetary penalties, made civil and criminal penalties directly applicable to business associates, and gave state attorneys authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA laws and seek attorneys’ fees and costs.
+Added: In addition, there may be other federal, state and non-U.S.
+Added: laws which govern the privacy and security of health and other personal information and which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
+Added: • 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, certain other licensed health care practitioners and teaching hospitals.
Manufacturers are also required to disclose ownership and investment interest held by physicians and their immediate family members.
1 unchanged sentence
• Federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers.
−Removed: • the Foreign Corrupt Practices Act ("FCPA"), which prohibits companies and their intermediaries from making, or offering or promising to make, improper payments to non-U.S.
+Added: • The Foreign Corrupt Practices Act, which prohibits companies and their intermediaries from making, or offering or promising to make, improper payments to non-U.S.
officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment.
−Removed: Similarly, state privacy laws may be broader and require greater protections than HIPAA.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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).
+Added: Similarly, foreign and state privacy laws may be broader and require greater protections than HIPAA.
+Added: These data privacy and security laws may differ from each other and often are not pre-empted by HIPAA, which may complicate compliance efforts.
+Added: For example, 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.
+Added: CCPA provides for civil penalties for violations, as well as a private right of action for data breaches.
+Added: Further, the California Privacy Rights Act (“CPRA”) creates additional obligations with respect to processing and storing personal information.
We will continue to monitor developments related to the CPRA and anticipate additional costs and expenses associated with CPRA compliance.
−Removed: states also are considering omnibus privacy legislation and industry organizations regularly adopt and advocate for new standards in these areas.
−Removed: While the legislation and proposed regulations including the CCPA and CPRA contain an exception for certain activities that involve PHI subject to HIPAA, we cannot yet determine the impact the CCPA, CPRA or other such future laws, regulations and standards may have on our business.
+Added: states have also passed or are considering omnibus privacy legislation and industry organizations regularly adopt and advocate for new standards in these areas.
+Added: While the legislation and proposed regulations including the CCPA and CPRA contain an exception for certain activities that involve protected health information subject to HIPAA, we cannot yet determine the impact the CCPA, CPRA or other such future laws, regulations and standards may have on our business.
Additionally, we are subject to state equivalents of each of the healthcare laws described above, among others, some of which may be broader in scope and may apply to healthcare services reimbursed by any third-party payor, not just governmental payors, but also private insurers.
These laws are enforced by various state agencies and through private actions.
−Removed: Some states have passed laws that require pharmaceutical companies to comply with the April 2003 Office of Inspector General
−Removed: 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.
+Added: 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.
−Removed: State and foreign laws, including for example the European Union General Data Protection Regulation, which became effective May 2018, also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
−Removed: 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.
−Removed: 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.
−Removed: 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.
+Added: State and foreign laws, including the European Union General Data Protection Regulation, also govern the privacy and security of health information in some circumstances, many of which differ from other laws, thus complicating compliance efforts.
+Added: There are ambiguities as to what is required to comply with these state requirements and if we fail to comply with such requirements we could be subject to penalties.
+Added: In the U.S., 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.
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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.
−Removed: 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.
−Removed: 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.
−Removed: Accordingly, companies exclude these Part D beneficiaries from using co-pay coupons.
+Added: The CMS also requires individual market qualified health plans to accept third-party premium and cost-sharing payments from certain government-related entities.
+Added: Furthermore, the Office of Inspector General (“OIG”) of the HHS has warned manufacturers that they may be subject to sanctions under the federal AKS and/or civil monetary penalty laws if they do not take appropriate steps to exclude 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.
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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.
−Removed: 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.
+Added: The scope and enforcement of these laws is uncertain and subject to rapid change in the current environment of healthcare reform.
Federal and state enforcement has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry.
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In the EU, the General Data Protection Regulation (“GDPR”) governs the processing of personal data.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: In addition, further to the UK’s exit from the EU on January 31, 2020, the GDPR ceased to apply in the UK at the end of the transition period on December 31, 2020.
−Removed: However, as of January 1, 2021, the UK’s European Union (Withdrawal) Act 2018 incorporated the GDPR (as it existed on December 31, 2020 but subject to certain UK specific amendments) into UK law, referred to as the UK GDPR.
+Added: The GDPR imposes a broad range of strict requirements on companies subject to the GDPR, such as including requirements relating to having legal basis 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 in countries not deemed adequate by the EU and UK, 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 if there is no legal basis for processing, 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.
+Added: 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.
+Added: In addition, the UK’s European Union (Withdrawal) Act 2018 incorporated the GDPR (subject to certain UK specific amendments) into UK law, referred to as the UK GDPR.
The UK GDPR and the UK Data Protection Act 2018 set out the UK’s data protection regime, which is independent from but aligned to the EU’s data protection regime.
Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.
−Removed: 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.
The UK government has confirmed that personal data transfers from the UK to the EEA remain free flowing.
−Removed: To enable the transfer of personal data outside of the EEA or the UK, adequate safeguards must be implemented in compliance with European and UK data protection laws.
−Removed: On June 4, 2021, the EC issued new forms of standard contractual clauses for data transfers from controllers or processors in the EU/EEA (or otherwise subject to the GDPR) to controllers or processors established outside the EU/EEA (and not subject to the GDPR).
−Removed: The new standard contractual clauses replace the standard contractual clauses that were adopted previously under the EU Data Protection Directive.
−Removed: The UK is not subject to the EC’s new standard contractual clauses but has published a draft version of a UK-specific transfer mechanism, which, once finalized, will enable transfers from the UK.
−Removed: We will be required to implement these new safeguards when conducting restricted data transfers under the EU and UK GDPR and doing so will require significant effort and cost.
+Added: We will be required to implement certain safeguards detailed in these regulations when conducting restricted data transfers under the EU and UK GDPR and doing so will require significant effort and cost.
PRC Regulation
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The legal framework for the administration of pharmaceutical products in China was established by the Drug Administration Law of the PRC (the “DAL”).
−Removed: 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.
−Removed: 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.
−Removed: The Implementing Measures of the Drug Administration Law as amended in 2019 provides detailed implementation regulations for the DAL.
−Removed: The Revised DAL
−Removed: The DAL, revised in 2019 (the "rDAL"), embodies an expected regulatory trend to strengthen the life-cycle management of drugs, to balance the development of innovative drugs and generic drugs, and to enhance drug review and enforcement.
−Removed: It also reflects legislative efforts to address prominent problems of the pharmaceutical industry, such as counterfeit and substandard drugs and high drug prices.
−Removed: The rDAL contains a dedicated chapter on the Marketing Authorization Holder ("MAH") system.
−Removed: Subject to approval by the NMPA, MAHs will be allowed to transfer their marketing authorizations.
−Removed: It is uncertain whether the transferability of MAH will offer more flexibility in structuring cross-border transactions.
+Added: The DAL provides 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.
+Added: The Implementing Measures of the Drug Administration Law provides detailed implementation regulations for the DAL.
+Added: The DAL embodies a regulatory trend to strengthen the life-cycle management of drugs, to balance the development of innovative drugs and generic drugs, and to enhance drug review and enforcement.
+Added: It established the Marketing Authorization Holder (the “MAH”) system, and subject to approval by the NMPA, MAHs will be allowed to transfer their marketing authorizations.
+Added: However, to date, it remains uncertain whether the transferability of MAH will offer more flexibility in structuring cross-border transactions.
In addition, the implementation of the MAH system was accompanied by a range of new requirements for the MAHs.
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A foreign MAH is required to engage a local agent to fulfill the MAH’s obligations and the foreign MAH is subject to joint and several liability in the event of any wrongdoing.
−Removed: It is unclear how the scope of such joint liability will be defined.
−Removed: The rDAL no longer requires the certification for GCP, good supply practice ("GSP"), and GMP.
−Removed: However, drug manufacturers and drug distributors must still comply with current GMP and GSP requirements.
−Removed: Pursuant to the rDAL, NMPA
−Removed: 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.
−Removed: 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.
−Removed: The rDAL also requires MAHs, manufacturers, distributors, and medical institutions to establish and implement drug track and trace systems.
−Removed: The NMPA will issue related standards and regulations regarding drug track and trace system.
+Added: The DAL requires drug manufacturers and drug distributors to comply with current GMP and GSP requirements.
+Added: Pursuant to the DAL, NMPA and its local counterparts are directed to strengthen their surveillance of drug manufacturers and distributors, including through regular site inspections and unannounced checks, to ensure their compliance.
+Added: The NMPA has also been strengthening its regulation of clinical trial institutions by collaborating with the National Health Commission (the “NHC”), the chief healthcare regulator in China.
+Added: The Measures for the Administration of Drug Clinical Trial Institutions jointly issued by the NMPA and the NHC provides detailed requirements on how drug clinical trial institutions should comply with GCP, including, among others, that all drug clinical trial institutions are required to be registered on an online system and disclose their key information essential for compliance with GCP.
+Added: The DAL also requires MAHs, manufacturers, distributors, and medical institutions to establish and implement drug track and trace systems.
+Added: The Measures for the Quality Supervision of Drug Commercialization and Use established the requirements and standards for the drug track and trace system.
A drug pharmacovigilance system will also be established to monitor, identify, evaluate and control adverse drug reactions and other possible drug-related problems.
−Removed: The rDAL creates an expanded access pathway for investigational drugs under which a company sponsor of a clinical trial in China can apply to establish an expanded access treatment program for patients with life-threatening disease who otherwise do not satisfy the inclusion criteria of a clinical trial.
+Added: The Good Pharmacovigilance Practices provides detailed requirements on MAH’s pharmacovigilance obligations.
+Added: The DAL creates an expanded access pathway for investigational drugs under which a company sponsor of a clinical trial in China can apply to establish an expanded access treatment program for patients with life-threatening disease who otherwise do not satisfy the inclusion criteria of a clinical trial.
To quality for expanded access:
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and (5) the drug must be used within the clinical trial institution and used on patients with similar conditions.
−Removed: The rDAL also significantly increases and expands penalties for violations.
−Removed: Depending on various types of violations, the rDAL imposes different penalties, including warnings, confiscation of illegal gains, fines of up to RMB5 million (about $725,000) or up to 30 times of illegal gains, revocation of required business and operating licenses, certificates or approval documents for drugs, suspension of business, temporary (10 years) or permanent debarment of companies, institutions and responsible persons, and criminal liabilities in the case of serious violations.
−Removed: There are still uncertainties with respect to the interpretation and implementation of the rDAL.
−Removed: We plan to closely monitor the implementation of the rDAL and its impact on our operations in China.
+Added: The DAL provides heavy penalties for violations.
+Added: Depending on various types of violations, the DAL imposes different penalties, including warnings, confiscation of illegal gains, fines of up to RMB5 million (about $725,000) or up to 30 times of illegal gains, revocation of required business and operating licenses, certificates or approval documents for drugs, suspension of business, temporary (10 years) or permanent debarment of companies, institutions and responsible persons, and criminal liabilities in the case of serious violations.
+Added: The interpretation and implementation of the DAL have been evolving overtime.
+Added: We plan to closely monitor the implementation of the DAL and its impact on our operations in China.
Regulatory Authorities and Government Reorganization
In China, the NMPA is the primary regulator for pharmaceutical products and businesses.
−Removed: The agency was formed from the prior China Food and Drug Administration ("CFDA") in 2018 as part of a complete government reorganization.
−Removed: The NMPA is no longer an independent agency.
−Removed: 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.
−Removed: 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).
+Added: It is a sub-agency of the State Administration for Market Regulation (the “SAMR”), which is responsible for, in addition to drug regulation, consumer protection, advertising, anticorruption, antitrust, fair competition and intellectual property.
+Added: The NMPA 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 CDE, which remains under the NMPA, conducts the technical evaluation of each drug and biologic application for safety and efficacy.
−Removed: The National Health Commission ("NHC") is China’s chief healthcare regulator.
−Removed: 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.
−Removed: The NHC plays a significant role in drug reimbursement.
−Removed: Furthermore, the NHC and its local counterparts at or below the provincial-level of local government also oversee and organize public medical institutions’ centralized bidding and procurement programs for pharmaceutical products.
+Added: The NHC is China’s chief healthcare regulator.
+Added: It is primarily responsible for overseeing the operation of medical institutions (including clinical trial sites) and regulating the licensure of hospitals and other medical personnel.
+Added: The NHSA is the primary regulator overseeing national medical insurance and related drug reimbursement schemes, including, among others, the National Drug Reimbursement Price Negotiations, which have significant impact on innovative drugs’ prices in China.
+Added: The NHSA and its local counterparts at or below the provincial level of local government also oversee and organize public medical institutions’ centralized bidding and procurement programs for pharmaceutical products.
This is the primary way that public hospitals and their internal pharmacies procure drugs.
−Removed: Also, as part of the 2018 reorganization, the PRC government formed the State Medical Insurance Bureau which focuses on regulating reimbursement under state-sponsored insurance plans.
Preclinical and Clinical Development
The NMPA requires preclinical data to support registration applications for new drugs.
−Removed: Preclinical work, including safety assessment studies, must meet the GLP standards, issued in 2003 and amended in 2017.
−Removed: The rDAL requires the NMPA to accredit GLP labs, and that nonclinical studies of chemical drug substances and preparations and biologics that are not yet marketed in China be conducted in GLP-certified labs.
+Added: Preclinical work, including safety assessment studies, must meet the GLP’s standards.
+Added: The DAL requires the NMPA to accredit GLP labs, and that nonclinical studies of chemical drug substances and preparations and biologics that are not yet marketed in China be conducted in GLP-certified labs.
There are no approvals required from the NMPA to conduct preclinical studies.
−Removed: 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.
−Removed: Applicants for this certificate must satisfy a number of conditions,
−Removed: including (1) the environment and facilities for lab animals’ living and propagating must satisfy national requirements;
+Added: 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, the Administrative Measures on Good Practice of Experimental Animals, and the Administrative Measures on the Certificate for Experimental Animals (Trial).
+Added: 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;
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Therapeutic biologics follow a similar categorization, with Category 1 being new to the world.
−Removed: Like with small molecule drugs, Category 1 is for innovative biologics that have not been approved inside or outside of China.
Biosimilars are under Category 3.
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Zanubrutinib, pamiparib and tislelizumab have been approved by the NMPA as Category 1 drugs.
+Added: Amgen’s BLINCYTO, XGEVA, and KYPROLIS, as well as EUSA’s QARZIBA and SYLVANT have all been approved by the NMPA as Category 1 drugs.
Expedited Programs
Priority Evaluation and Approval Programs to Encourage Innovation
−Removed: The NMPA has adopted several expedited review and approval mechanisms since 2009 and created additional expedited programs in recent years that are intended to encourage innovation.
−Removed: Applications for these expedited programs can be submitted after the CTA is admitted for review by the CDE.
−Removed: The NMPA’s Drug Registration Rules effective from July 1, 2020 ("DRR") provides certain categories of drugs that may be eligible for priority status, among which, the following may be particularly relevant for us:
+Added: The NMPA has adopted several expedited review and approval mechanisms that are intended to encourage innovation.
+Added: Applications for these expedited programs can be submitted after the clinical trial application is admitted for review by the CDE.
+Added: The NMPA’s Drug Registration Rules (“DRR”) provide certain categories of drugs that may be eligible for priority status, among which, the following may be particularly relevant for us:
(1) drugs that are clinically and urgently needed but insufficient in supply;
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If admitted to one of these expedited programs, an applicant will be entitled to more frequent and timely communication with reviewers at the CDE, expedited review and approval, and more agency resources throughout the approval process.
−Removed: Amgen's sBLA for BLINCYTO has been accepted by the CDE and granted priority status.
−Removed: Our sNDA for tislelizumab for MSI-H/dMMR solid tumor has been accepted by the CDE and granted priority status.
Conditional Approval
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(1) drugs that treat life threatening illnesses for which there are no effective treatment or preventive methods, but their clinical trials already have the data to prove efficacy and their clinical value is predictable, (2) drugs that are urgently needed for public health reasons, and their clinical trials already have the data to prove efficacy and their clinical value is predictable;
−Removed: or (3) vaccines that are urgently needed for major public health emergencies or otherwise deemed by the National Health Commission to be urgently needed, and it is concluded upon evaluation that their benefits outweigh their risks.
+Added: or (3) vaccines that are urgently needed for major public health emergencies or otherwise deemed by the NHC to be urgently needed, and it is concluded upon evaluation that their benefits outweigh their risks.
Following approval, the MAH is required to take risk mitigation measures and complete a post-market study as required by the NMPA within a prescribed timeline.
−Removed: BRUKINSA received conditional approval for the treatment of MCL in adult patients who have received at least one prior therapy, CLL or SLL in adult patients who have received at least one prior therapy, and for adult patients with WM who have received at least one prior therapy.
−Removed: Tislelizumab received conditional approval as a treatment for patients with cHL who have received at least two prior therapies and as a treatment for patients with locally advanced or metastatic UC, a form of bladder cancer, with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, and for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with at least one systemic therapy.
−Removed: 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.
−Removed: XGEVA received conditional approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of the bone
−Removed: (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.
−Removed: BLINCYTO received conditional approvals for the treatment of both adult and pediatric patients with R/R B-cell precursor acute lymphoblastic leukemia.
+Added: BRUKINSA received conditional approval for the treatment of MCL in adult patients who have received at least one prior therapy, CLL or SLL in adult patients who have received at least one prior therapy (converted to regular approval), and for adult patients with WM who have received at least one prior therapy (converted to regular approval).
+Added: Tislelizumab received conditional approval as a treatment for patients with cHL who have received at least two prior therapies and as a treatment for patients with locally advanced or metastatic UC, a form of bladder cancer, with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, and for the treatment of patients with HCC who have been previously treated with at least one systemic therapy (converted to regular approval).
+Added: PARTRUVIX received conditional approval for the treatment of patients with gBRCA mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy.
+Added: XGEVA received conditional approval for the treatment of adults and skeletally mature adolescents with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity (converted to regular approval) and for the prevention of SREs in patients with bone metastases from solid tumors and in patients with MM.
+Added: BLINCYTO received conditional approvals for the treatment of both adult and pediatric patients with R/R CD19-positive B-cell precursor acute lymphoblastic leukemia (adult indication converted to regular approval).
KYPROLIS received conditional approval for the treatment of adult patients with R/R multiple myeloma.
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Applicants of drugs designated as breakthrough therapies will be entitled to direct communications with CDE at key states during the clinical trials and may seek CDE’s opinion on study progress.
−Removed: Amgen's KRAS G12C inhibitor sotorasib was granted BTD in China for patients with KRAS p.G12C -mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy.
BRUKINSA as a treatment for adult patients with CLL/SLL was granted BTD in China.
ZW25 (zanidatamab) as a treatment for R/R HER2-expressing biliary tract cancer was granted BTD.
−Removed: New Policies on Expediting Approval of Imported Oncology Drugs
+Added: Policies on Expediting Approval of Imported Oncology Drugs
The PRC government continues to establish measures and incentives to promote the development and swifter approval of marketing for oncology and other innovative drugs.
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The materials required for this application and the data requirements are determined by the registration category.
−Removed: The NMPA has taken a number of steps to increase efficiency for approving CTAs, and it has also significantly increased monitoring and enforcement of GCP to ensure data integrity.
+Added: The NMPA has taken a number of steps to increase efficiency for approving clinical trial applications, and it has also significantly increased monitoring and enforcement of GCP to ensure data integrity.
Clinical Trial Approval
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In addition to a standalone China trial to support development, imported drug applicants may include Chinese clinical sites as part of an international multicenter trial (“IMCT”).
−Removed: Domestically manufactured drugs are not subject to foreign approval requirements, and in contrast to prior practice, the NMPA has decided to permit those drugs to conduct development via an IMCT as well.
−Removed: The rDAL has now also adopted an implied approval system for clinical trials of new drugs.
+Added: Domestically manufactured drugs are not subject to foreign approval requirements and the NMPA permits those drugs to conduct development via an IMCT as well.
+Added: The DAL has now also adopted an implied approval system for clinical trials of new drugs.
Trials can proceed if after 60 business days, the applicant has not received any objections from the CDE, as opposed to the lengthier previous clinical trial pre-approval process in which the applicant had to wait for affirmative approval.
−Removed: The rDAL also expands the number of trial sites by abolishing the GCP accreditation system and requiring trial sites to follow a more simplified notification procedure.
−Removed: New Policies on Clinical Value-Oriented R&D for Oncology Drugs
−Removed: The NMPA finalized in November 2011 the Guideline on Clinical Value-Oriented Research and Development for Oncology Drugs, as part of its policies intended to encourage the research and development of innovative oncology drugs with significant clinical value, and discourage repeated research and development of “me-too” drugs with minimal or no clinical value to patients.
+Added: The DAL also expands the number of trial sites by abolishing the GCP accreditation system and requiring trial sites to follow a more simplified notification procedure.
Clinical Trial Register
Clinical trials conducted in China must be registered and published through the Drug Clinical Trial Information Platform (http://www.chinadrugtrials.org.cn).
−Removed: 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.
−Removed: If the foregoing pre-registration and registration is not
−Removed: 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.
+Added: Applicants 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.
+Added: If the foregoing pre-registration and registration is not obtained within three years, the clinical trial approval automatically expires.
Human Genetic Resources Regulation
−Removed: The Regulation on the Administration of Human Genetic Resources ("HGR Regulation") became effective on July 1, 2019.
−Removed: The HGR Regulation applies to all human genetic resources ("HGR")-related activities for R&D purposes, including sampling, biobanking, use of HGR materials and associated data in China, and the provision or sharing of such materials or data with foreign parties.
−Removed: The HGR Regulation applies to foreign parties, including foreign entities and entities established or actually controlled by foreign entities and individuals.
+Added: The Regulation on the Administration of Human Genetic Resources (“HGR Regulation”) applies to all human genetic resources (“HGR”)-related activities for R&D purposes, including sampling, biobanking, use of HGR materials and associated data in China, and the provision or sharing of such materials or data with non-PRC parties.
As BeiGene, Ltd.
is a Cayman Islands company, we and our activities in China are subject to the HGR Regulation.
−Removed: Such foreign parties seeking access to China’s HGRs for scientific research, including clinical trials intended to support marketing approval of drugs and medical devices in China, must do so only through collaborations with Chinese parties, such as Chinese hospitals.
−Removed: The HGR Regulation prohibits foreign parties from independently sampling or biobanking any China HGR in China and requires approval for the sampling of certain HGR and biobanking of all HGR by Chinese parties.
+Added: Such non-PRC parties seeking access to China’s HGRs for scientific research, including clinical trials intended to support marketing approval of drugs and medical devices in China, must do so only through collaborations with Chinese parties, such as Chinese hospitals.
+Added: The HGR Regulation prohibits non-PRC parties from independently sampling or biobanking any China HGR in China and requires approval for the sampling of certain HGR and biobanking of all HGR by Chinese parties.
Any cross-border transfer of the HGR materials, either under an international collaboration or as a direct export, must be on an as-needed basis and requires approval.
−Removed: In addition, providing HGR data to foreign parties requires a record filing.
−Removed: Another significant change is the HGR Regulation replaced the advance approval requirement with a record-filing procedure for international collaborations on clinical trials intended to support marketing approval of drugs in China that do not transfer HGR materials abroad, while the advance approval requirement still applies if such trials involve export of HGR materials or the collection, testing, analysis or disposals of HGR samples during the trials are not solely conducted at the clinical trial sites.
+Added: In addition, providing HGR data to non-PRC parties requires a record filing.
+Added: The HGR Regulation provides a record-filing procedure for international collaborations on clinical trials intended to support marketing approval of drugs in China that do not transfer HGR materials abroad, while the advance approval requirement still applies if such trials involve export of HGR materials or the collection, testing, analysis or disposal of HGR samples during the trials are not solely conducted at the clinical trial sites.
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.
−Removed: 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.
+Added: The HGR Regulation requires parties to 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.
−Removed: 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.
−Removed: We expect that HGR-related activities will receive greater attention and focus from regulators going forward.
+Added: The HGR Regulation also imposes severe 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.
+Added: The Implementing Rules for the HGR Regulation (the “HGR Implementing Rules”) provide several critical clarifications.
+Added: HGR data is narrowed down to cover only the data derived from HGR materials and gene-irrelevant clinical data, image data, protein data, and metabolic data are expressly excluded.
+Added: The use of the term non-PRC parties is also further clarified by elaborating that (1) “actual control” by non-PRC entities/individuals is interpreted to include not only being controlled through equity interests but also investment or contractual arrangements, which may cover variable interest entities (“VIEs”), and (2) companies incorporated in Hong Kong Special Administration Region (“SAR”) and Macau SAR but essentially controlled by Chinese domestic entities are not viewed as non-PRC parties.
+Added: The industry guidance provides more clarifications from practice perspective.
+Added: Notably, among others, (1) the non-PRC entity operating the electronic data capture system for an in-China trial is no longer regarded as a non-PRC party, (2) for gene-related scientific studies, if non-PRC entities do not substantively participate in such studies, nor obtain any study data, then such studies are no longer subject to the HGR regulation;
+Added: and (3) human urine, feces, blood plasma, and blood serum are expressly excluded from the scope of HGR materials.
Trial Exemptions and Acceptance of Foreign Data
The NMPA may be flexible on the requirements of trials and data generated in China, depending on the drug and the existing data.
−Removed: The NMPA has granted waivers for all or part of trials, and has stated that it will accept data generated abroad (even if not part of a global study), including early phase data, that meets its requirements.
−Removed: 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”).
+Added: The NMPA has granted waivers for all or part of trials and stated that it will accept data generated abroad (even if not part of a global study), including early phase data, that meets its requirements.
+Added: 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.
Sponsors must be attentive to potentially meaningful ethnic differences in the subject population.
−Removed: The NMPA now permits, and its predecessor agencies have permitted on a case-by-case basis in the past, drugs approved outside of China to be approved in China on a conditional basis without the need for pre-approval clinical trials in China.
−Removed: Specifically, in 2018, the NMPA established a program permitting drugs that have been approved within the last ten years in the United States, EU or Japan to be approved in China without local clinical trials if they (1) prevent or treat orphan diseases, (2) prevent or treat serious life-threatening illnesses for which there is either no effective therapy in China, or for which the foreign-approved drug would have clear clinical advantages.
+Added: The NMPA permits drugs approved outside of China to be approved in China on a conditional basis without the need for pre-approval clinical trials in China.
+Added: Specifically, in 2018, the NMPA established a program permitting drugs that have been approved within the last ten years in the U.S., EU or Japan to be approved in China without local clinical trials if they (1) prevent or treat orphan diseases, (2) prevent or treat serious life-threatening illnesses for which there is either no effective therapy in China, or for which the foreign-approved drug would have clear clinical advantages.
Applicants for such conditional approvals will be required to establish a risk mitigation plan and may be required to complete trials in China after the drug is approved.
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Phase 3 (often the pivotal study) refers to clinical trials to further verify the drug candidate’s therapeutic efficacy and safety on patients with target indication(s) and ultimately provide sufficient evidence for the review of a drug registration application.
−Removed: The NMPA requires that the different phases of clinical trials in China receive ethics committee approval and comply with GCP.
+Added: The NMPA requires that the different phases of clinical trials in China receive ethics committee approval (with exemptions for certain specific circumstances, such as studies utilizing public information or anonymized data) and comply with GCP.
The NMPA conducts inspections on clinical trials conducted in China to assess GCP compliance and may refuse to approve the drug if it finds substantial issues in the trials.
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Pharmaceutical packaging must comply with national and professional standards.
−Removed: If there is no national or professional standard available, companies may formulate and implement its own standards after obtaining the approval of the provincial administration for medical products or bureau of standards.
+Added: If there is no national or professional standard available, companies may formulate and implement their own standards after obtaining the approval of the provincial administration for medical products or bureau of standards.
Changes in such approved packaging standards need to be re-approved.
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For domestically manufactured drugs, NDA sponsors must submit data derived from the submitted drugs in support of their approval.
−Removed: Under the rDAL, upon approval of the registration application, the NMPA will issue a drug registration certificate to the applicant which is in fact the marketing approval of the drug, and the applicant is no longer required to be equipped with relevant manufacturing capability.
+Added: Under the DAL, upon approval of the registration application, the NMPA will issue a drug registration certificate to the applicant which is in fact the marketing approval of the drug, and the applicant is no longer required to be equipped with relevant manufacturing capability.
Manufacturing and Distribution
−Removed: All facilities that manufacture drugs in China must receive a drug manufacturing license with an appropriate “scope of manufacturing” from the local drug regulatory authority.
−Removed: This license must be renewed every five years, and the manufacturing facility is also required to be in compliance with GMP.
+Added: All facilities that manufacture drugs in China must receive a Drug Manufacturing License (“DML”) with an appropriate “scope of manufacturing” from the local drug regulatory authority.
+Added: This license must be renewed every five years, and the manufacturing facility is also required to comply with GMP.
+Added: MAHs holding a Type B DML are allowed to contract manufacturing and must undertake the quality management obligations.
+Added: NMPA has been increasing its regulatory oversight and control over contract manufacturing activities in China by way of imposing more specific and higher regulatory compliance requirements in terms of personnel, quality management system, and oversight of CMOs on MAHs.
+Added: For instance, NMPA released a Guidance on Onsite Inspection of Contract Manufacturing Activities by Drug MAHs in October 2023, in which over 60 inspection items are set for issuing and maintaining Type B DML.
Similarly, to conduct sales, importation, shipping and storage, a company must obtain a Drug Distribution License (“DDL”) from the local drug regulatory authority, subject to renewal every five years.
−Removed: As with GMPs, companies are required to be in compliance with GSP.
−Removed: One exception is that the rDAL and relevant implementation rules allow the MAH to conduct wholesales of its drugs directly without holding a separate DDL for wholesale, however, a retail DDL would still be required if the MHA intends to conduct direct retail to patients.
+Added: As with GMPs, companies are required to comply with GSP.
+Added: One exception is that the DAL and relevant implementation rules allow the MAH to conduct wholesales of its drugs directly without holding a separate DDL for wholesale, however, a retail DDL would still be required if the MHA intends to conduct direct retail to patients.
China has developed a “Two-Invoice System” to control distribution of prescription drugs.
−Removed: The “Two-Invoice System” generally requires that no more than two invoices may be issued throughout the distribution chain, with one from the manufacturer to a distributor and another from the distributor to the end-user hospital.
+Added: This system generally requires that no more than two invoices may be issued throughout the distribution chain, with one from the manufacturer to a distributor and another from the distributor to the end-user hospital.
This excludes the sale of products invoiced from the manufacturer to its wholly-owned or controlled distributors, or for imported drugs, to their exclusive distributor, or from a distributor to its wholly-owned or controlled subsidiary (or between the wholly-owned or controlled subsidiaries).
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Compliance with the Two-Invoice System is a prerequisite for pharmaceutical companies to participate in procurement processes with public hospitals, which currently provide most of China’s healthcare.
−Removed: Manufacturers and distributors that fail to implement the Two-Invoice System may lose their qualifications to participate in the bidding process.
−Removed: Non-compliant manufacturers may also be blacklisted from engaging in drug sales to public hospitals in a locality.
+Added: Manufacturers and distributors that fail to implement this system may lose their qualifications to participate in the bidding process or be blacklisted from engaging in drug sales to public hospitals in a locality.
Post-Marketing Surveillance
−Removed: Under the rDAL, the MAH of a drug is ultimately responsible for pharmacovigilance, including quality assurance, adverse reaction reporting and monitoring, and product recalls.
+Added: Under the DAL, the MAH of a drug is ultimately responsible for pharmacovigilance, including quality assurance, adverse reaction reporting and monitoring, and product recalls.
Distributors and user entities (e.g., hospitals) are also required to report, in their respective roles, adverse reactions of the products they sell or use, and assist the MAH with any product recalls.
−Removed: 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.
+Added: An MAH for a drug that is currently under the new drug monitoring period has to report all adverse drug reactions (as opposed to just serious adverse reactions) for that period.
Advertising and Promotion of Pharmaceutical Products
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Regulatory Intellectual Property Protections
−Removed: The amendments to the PRC Patent Law (the “Amended PRC Patent Law”) became effective on June 1, 2021.
−Removed: The Amended PRC Patent Law contains both patent term extension and a mechanism for early resolution of patent disputes, which may be comparable to patent linkage in the United States.
−Removed: However, the provisions for patent term extension are unclear and/or remain subject to the approval of implementing regulations that are still in draft form or have not yet been proposed, leading to uncertainty about its scope and implementation.
−Removed: Non-Patent Exclusivities
−Removed: Regulatory Data Protection
−Removed: The Innovation Opinion provided a foundation to improve and implement a system for regulatory data protection to protect innovative drugs.
−Removed: This protection will be available for undisclosed clinical trial data of drugs falling into the following categories:
+Added: The amendments to the PRC Patent Law (the “Amended PRC Patent Law”) provides a cause of action to allow a patent holder to initiate a declarative action during the regulatory review process of a drug to determine whether the drug falls within the patent scope, which may be comparable to the patent linkage system in the U.S.
+Added: The system requires that the NMPA continue to review the potentially infringing follow-on application during any lawsuit by the innovator.
+Added: However, the NMPA may not approve the follow-on application pending resolution of the patent litigation in favor of the follow-on application or for a specified period of time, whichever is shorter.
+Added: The Amended PRC Patent Law also provides patent term extension, similar to the U.S., for the patent term lost during the regulatory review process of a new drug upon the patent holder’s request.
+Added: The extended term shall not exceed five years, and the total patent term after market entry of the new drug shall not exceed 14 years.
+Added: However, the provisions for patent term extension are unclear and/or remain subject to the approval of implementing regulations that are still in draft form, leading to uncertainty about the scope of implementation.
+Added: Additionally, the Innovation Opinion provided a foundation to improve and implement a system for regulatory data protection to protect innovative drugs.
+Added: This protection is 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.
−Removed: In the Trade Agreement, China has committed to providing for effective protection of undisclosed clinical trial or other data submitted as a condition of marketing approval.
The NMPA has published draft regulations for public comment that would set regulatory data protection for innovative small molecule drugs at six years and for innovative therapeutic biologics at 12 years;
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The proposed regulations also call for a reduction in exclusivity if the marketing application is filed in China based solely on overseas clinical data with no Chinese subjects (75% reduction) or based on supplemental “China clinical trial data” (50% reduction).
−Removed: Information about the exclusivity term will be included in a Marketed Drug List (similar to the Orange Book in the US) at the time of approval.
+Added: Information about the exclusivity term will be included in a Marketed Drug List (similar to the Orange Book in the U.S.) at the time of approval.
Some mechanics of these proposed rules are not yet clear, and it is not certain when the proposed rules will be finalized.
−Removed: Patent-Related Protections
−Removed: Patent Linkage
−Removed: The Amended PRC Patent Law provides a cause of action to allow a patent holder to initiate a declarative action during the regulatory review process of a drug to determine whether the drug falls within the patent scope, which may be comparable to the patent linkage system in the United States.
−Removed: The system requires that the NMPA continue to review the potentially infringing follow-on application during any lawsuit by the innovator.
−Removed: However, the NMPA may not approve the follow-on application pending resolution of the patent litigation in favor of the follow-on application or for a specified period of time, whichever is shorter.
−Removed: Patent Term Extension
−Removed: The Amended PRC Patent Law provides patent term extension, similar to the United States, for the patent term lost during the regulatory review process of a new drug upon the patent holder’s request.
−Removed: The extended term shall not exceed five years, and the total patent term after market entry of the new drug shall not exceed 14 years.
−Removed: However, the provisions for patent term extension are unclear and/or remain subject to the approval of implementing regulations that are still in draft form, leading to uncertainty about the scope of implementation.
Reimbursement and Pricing
+Added: China regulates drug prices mainly by establishing a consolidated procurement mechanism, restructuring medical insurance reimbursement standards and strengthening regulation of medical and pricing practices, as discussed below.
+Added: National Reimbursement Drug List
China’s national medical insurance program currently consists of two fundamental sub-programs:
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Factors that affect the inclusion of a pharmaceutical product in the NRDL include whether the product is used in large volumes and commonly prescribed for clinical use in the PRC and whether it is considered to be important in meeting the basic healthcare needs of the general public.
−Removed: Since 2016, special consideration has been given to, among others, innovative drugs with high clinical value and drugs for serious diseases.
+Added: Historically, 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 exclusive drugs with high clinical demands and proven effectiveness for price cuts in exchange for inclusion into the NRDL.
−Removed: 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.
+Added: The version of the NRDL released in 2023 (effective from January 1, 2024) covers approximately 3,088 drugs in total, including 121 new drugs listed for which the prices were determined through negotiations between the drug companies and government.
China has been pursuing a policy of expediting the addition of innovative oncology drugs to this list.
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BRUKINSA (zanubrutinib), tislelizumab, and XGEVA (120-mg denosumab) have been included in the NRDL since 2020.
−Removed: PARP inhibitor pamiparib has been included in the NRDL since 2022.
−Removed: KYPROLIS was included for the first time in the NRDL in January 2023, which will take effect on March 1, 2023.
−Removed: Government Price Controls
−Removed: China has abolished its previous government-led pricing system for drugs, and lifted the maximum retail price for most drugs, including drugs reimbursed by government medical insurance funds, patented drugs, and some other drugs.
−Removed: The government now regulates prices mainly by establishing a consolidated procurement mechanism, restructuring medical insurance reimbursement standards and strengthening regulation of medical and pricing practices, as discussed below.
+Added: PARP inhibitor PARTRUVIX (pamiparib) has been included in the NRDL since 2021.
+Added: KYPROLIS has been included in the NRDL since 2022.
+Added: SYLVANT and BAITUOWEI were included in the NRDL in December 2023, which took effect on January 1, 2024.
Centralized Procurement and Tenders
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The committee members assess the bids based on a number of factors, including bid price, product quality, clinical effectiveness, product safety, level of technology, the manufacturer’s qualifications and reputation, after-sale services and innovation.
−Removed: Over the last decade, the government has employed various methods to improve the affordability of drugs.
−Removed: In 2009, the central government announced a campaign to implement a “zero markup” policy on essential drugs among basic healthcare institutions, which has been fully implemented nationwide.
+Added: Since 2018, the government implemented a “zero markup” policy on all drugs among all public healthcare institutions nationwide.
In addition, some local governments have begun to allow medical institutions to collectively negotiate with manufacturers for a second price to further lower the already agreed bid price.
The Two-Invoice System, described above, is also designed to reduce price mark-ups brought about by multi-tier distribution chains.
−Removed: In 2019, the government approved a volume-based, centralized drug procurement program in an effort to deepen the reform of the medical and health sector and optimize the pricing of drugs.
+Added: Since 2019, the government adopted a volume-based, centralized drug procurement program to optimize the pricing of drugs.
Drugs are selected from generic brands for volume-based, centralized drug procurement.
−Removed: The selected drugs must pass the equivalence evaluation on quality and efficacy.
−Removed: The program is aimed at further lowering drug costs for patients, reducing transaction costs for enterprises, regulating drug use by institutions, and improving the centralized drug procurement and pricing system.
+Added: The selected drugs must pass the bio-equivalence evaluation on quality and efficacy.
All approved enterprises that produce drugs on the procurement list in China may participate.
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Pharmaceutical companies operating in China are subject to changing regulations under many other laws and regulations administered by governmental authorities at the national, provincial and municipal levels, some of which are or may become applicable to our business.
−Removed: For example, regulations control the confidentiality of patient medical information and the circumstances under which patient medical information may be released for inclusion in our information systems or released by us to third parties.
−Removed: The privacy of human subjects in clinical trials is also protected under regulations.
−Removed: For example, clinical trial case report forms must avoid disclosing names of human subjects.
+Added: For example, regulations controlling the confidentiality of patient medical information and the circumstances under which patient medical information may be released for inclusion in our information systems or released by us to third parties.
+Added: The privacy of human subjects in clinical trials is also protected by privacy laws such as the Personal Information Protection Law.
These laws and regulations governing both the disclosure and the use of confidential patient medical information may become more restrictive in the future, including restrictions on transfer of healthcare data.
−Removed: The Cybersecurity Law that took effect in 2017 designates healthcare as a priority area that is part of critical information infrastructure, and China’s cyberspace administration is working to finalize a draft rule on cross-border transfer of personal information.
+Added: The Cybersecurity Law designates healthcare as a priority area that is part of critical information infrastructure, and China’s cyberspace administration has been working to finalize the regulatory regime on cross-border transfer of personal information.
PRC Regulation of Foreign Investment
−Removed: The Foreign Investment Law of the PRC (the “Foreign Investment Law”) and its implementing rules (the “Implementing Rules”) took effect in 2020 and replaced previous laws and regulations governing foreign investment in China.
−Removed: The Foreign Investment Law and Implementing Rules establish a basic framework for access to, and the promotion and administration of foreign investments in China.
−Removed: They reflected China’s legislative efforts to rationalize China’s foreign investment regulatory regime in line with prevailing international practice and to unify legal requirements for both foreign and domestic investments.
−Removed: The Implementing Rules further clarified that China would encourage and promote foreign investment, protect the lawful rights and interests of foreign investors, and continue to improve the foreign investment environment in China.
+Added: The Foreign Investment Law of the PRC (the “Foreign Investment Law”) and its implementing rules (the “Implementing Rules”) establish a basic framework for access to, and the promotion and administration of foreign investments in China.
The Foreign Investment Law establishes a pre-entry national treatment and negative list system for the administration of foreign investments.
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Industries not listed in these two categories are generally deemed “permitted” for foreign investments unless specifically restricted by other applicable PRC laws or regulations.
−Removed: Pursuant to the 2022 Encouraged Industry Catalogue, the research, development and manufacture of innovative oncology drugs and certain other types of pharmaceutical products belongs to the encouraged industries for foreign investment.
+Added: Pursuant to the 2022 Encouraged Industry Catalogue, the research, development and manufacture of innovative oncology drugs, cell therapies, and certain other types of pharmaceutical products belongs to the encouraged industries for foreign investment.
+Added: PRC Antitrust Regulation
+Added: China’s anti-trust regulatory regime is founded on the Anti-Monopoly Law (the “AML”) (last amended in 2022) and supplemented by several implementation rules.
+Added: The AML in general restricts monopolistic practices including concentration of undertakings, horizontal and vertical monopolistic agreements, and certain activities of market dominance abuse.
+Added: The AML provides heavy penalties for violations, including warnings, confiscation of illegal gains, a fine ranging up to 50% of the preceding year’s turnover, revocation of required business and operating licenses, suspension of business, and even criminal liabilities.
+Added: The SAMR is the chief regulator of anti-trust law in China, and the pharmaceutical sector has been one of its focused enforcement area for years.
+Added: For example, in 2021, a local drug company was found to have engaged in resale price maintenance (“RPM”) practices and fined up to RMB 764 million, and in 2023, another local drug company was also fined RMB 12.64 million for RPM.
Regulations Relating to Product Liability
−Removed: Under a law which took effect in 2021, a defective product which causes property damage or physical injury to any person may subject the manufacturer or vendor of such product to civil liability for such damage or injury.
−Removed: Additionally, China's Product Quality Law, first adopted in 1993 and amended in 2018, governs the supervision and administration of product quality, aiming to protect the rights end-users and consumers.
−Removed: According to the Product Quality Law, manufacturers is liable for the quality of products produced by them, and sellers are required take measures to ensure the quality of the products sold by them.
+Added: Under current law, a defective product which causes property damage or physical injury to any person may subject the manufacturer or vendor of such product to civil liability for such damage or injury.
+Added: Additionally, China’s Product Quality Law provides that manufacturers are liable for the quality of products produced by them, and sellers are required take measures to ensure the quality of the products sold by them.
A manufacturer is liable for compensating for any bodily injury or property damage resulting from product defects unless the manufacturer is able to prove that:
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A person who is injured or whose property is damaged by the defects in the product may claim compensation from the manufacturer or the seller.
+Added: Regulations Relating to Technology Export Control
+Added: Import and export of technologies for civilian use are regulated under the PRC Administrative Regulations on Technology Import and Export (the “TIER”).
+Added: Technology export is broadly defined under Chinese law to encompass any cross-border transfer of technologies from a Chinese entity to overseas – whether by way of patent assignments, patent licenses, software licenses, transfers of technical know-how, or the provision of technical services, or by any other means.
+Added: TIER divides technology export into the categories of (1) “prohibited” technologies, which cannot be exported outside China (2) “restricted” technologies, which requires approvals from the relevant Chinese authority, and (3) “unrestricted” technologies, which requires filing of proper transaction documents with the authority.
+Added: The “prohibited” and “restricted” technologies are defined by the Catalogue of Technologies Prohibited or Restricted from Export (the “Catalogue”).
+Added: The latest Catalogue, which was issued on December 21, 2023, included “cell cloning and gene editing technologies used in humans” into the prohibited list.
+Added: It still remains unclear how the Chinese government would eventually enforce such prohibition on technology control.
+Added: We plan to closely monitor China’s legislative and regulatory evolvement in this area and its potential impact on our operations in China.
Regulations Relating to Commercial Bribery
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Regulations Relating to Foreign Exchange
−Removed: The Foreign Exchange Administration Regulations are the principal regulations governing foreign currency exchange in China.
−Removed: Under the PRC foreign exchange regulations, payments of current account items, such as profit distributions and trade and service-related foreign exchange transactions, may be made in foreign currencies without prior approval from the State Administration of Foreign Exchange ("SAFE") by complying with certain procedural requirements.
+Added: The Foreign Exchange Administration Regulations govern foreign currency exchange in China.
+Added: Under these regulations, payments of current account items, such as profit distributions and trade and service-related foreign exchange transactions, may be made in foreign currencies without prior approval from the State Administration of Foreign Exchange (“SAFE”) by complying with certain procedural requirements.
In contrast, approval from or registration with appropriate government authorities or designated banks is required when RMB is to be converted into a foreign currency and remitted out of China to pay capital expenses such as the repayment of foreign currency-denominated loans.
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or paying expenses related to the purchase of real estate that is not for self-use, except for real estate enterprises.
−Removed: In 2017, new regulations were adopted which, among other things, relax the restrictions on foreign exchange inflow to further enhance trade and investment facilitation and tighten genuineness and compliance verification of cross-border transactions and cross-border capital flows.
−Removed: 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").
−Removed: 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.
+Added: Regulations have relaxed the restrictions on foreign exchange inflow to further enhance trade and investment facilitation and enhance genuineness and compliance verification of cross-border transactions and cross-border capital flows.
+Added: Furthermore, 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”) which 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.
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Regulations Relating to Overseas Listing
−Removed: 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.
−Removed: 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.
+Added: In 2023, the China Securities Regulatory Commission (the “CSRC”) released the Trial Administrative Measures of Overseas Securities Offering and Listing by Domestic (the “Overseas Listing Trial Measures”), and related guidelines requiring Chinese domestic companies’ overseas offerings and listings of equity securities be filed with the CSRC.
+Added: 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 that Chinese domestic companies that have already directly or indirectly offered and listed securities in overseas markets 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
−Removed: For other countries outside of the United States and the PRC, the requirements governing the conduct of clinical trials, drug licensing, pricing and reimbursement, and other matters impacting our business vary from country to country.
+Added: For other countries outside of the U.S.
+Added: and the PRC, the requirements governing the conduct of clinical trials, drug licensing, pricing and reimbursement, and other matters impacting our business vary from country to country.
In all cases, clinical trials must be conducted in accordance with GCP requirements, applicable regulatory requirements, and the ethical principles having their origin in the Declaration of Helsinki.
3 unchanged sentences
authority in the accounting firm’s jurisdiction (“Commission-Identified Issuers”).
−Removed: 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.
+Added: 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 U.S.
+Added: from being traded on any national securities exchange or over-the-counter markets in the U.S.
In December 2022, the Accelerating Holding Foreign Companies Accountable Act amended the HFCAA to shorten the three-year period to two years.
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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.
−Removed: On the same day, our audit committee approved the engagement of Ernst & Young LLP, located in Boston, Massachusetts, United States, as the Company’s
−Removed: 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.
+Added: On the same day, our audit committee approved the engagement of Ernst & Young LLP (U.S.) 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.
+Added: Ernst & Young LLP (U.S.) has continued to serve as our independent registered public accounting firm for the fiscal year ending December 31, 2023.
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.
1 unchanged sentence
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.
−Removed: 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.
+Added: Given that Ernst & Young LLP (U.S.) has served as the principal accountant to audit our consolidated financial statements to be filed with the SEC since 2022, 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 NASDAQ.
For a detailed description of risks related to our doing business in China and status under the HFCAA, see “Item 1A.
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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.
−Removed: 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.
−Removed: 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.
+Added: For example, the PRC government has recently published 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.
+Added: Furthermore, the PRC government has also 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.
−Removed: 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.
+Added: 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.
−Removed: 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.
+Added: In March 2023, the Overseas Listing Trial Measures, and five relevant guidelines issued by the CSRC took effect, 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.
−Removed: 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.
+Added: 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 U.S., 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.
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Flow of Funds with our PRC Operations
−Removed: 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.
−Removed: The intercompany flow of funds within the organization is effected through capital contributions and intercompany loans.
+Added: We are a holding company incorporated in the Cayman Islands with operations primarily conducted through direct and indirect subsidiaries in the U.S., China, United Kingdom, Switzerland and Australia.
+Added: The intercompany flow of funds within the organization is effected through capital contributions, intercompany loans, intercompany transfers of products and intellectual property, and cost reimbursements.
Since our formation in 2010, BeiGene, Ltd.
has raised over $10.0 billion in various public and private stock offerings as of December 31, 2023.
−Removed: Of this amount, $1.9 billion and RMB 18.6
−Removed: billion have been transferred as capital contributions to its operating subsidiaries;
−Removed: and $79 million and RMB 4.4 billion have been transferred as intercompany loans to its operating subsidiaries.
+Added: Of this amount, $1.9 billion and RMB 17.1 billion have been transferred as capital contributions to its operating subsidiaries.
+Added: As of December 31, 2023, BeiGene Ltd.
+Added: had intercompany loans outstanding of $1.6 billion and RMB 340 million 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.
−Removed: 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, 2023, BeiGene, Ltd.
2 unchanged sentences
has not received any dividends or distributions from its operating subsidiaries.
+Added: Please see the section of this Annual Report titled “Liquidity and Capital Resources” for further discussion.
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.
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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.
−Removed: However, conversion of RMB to other currencies are permitted for the purpose of dividends according to the PRC’s regulations on Foreign Exchange Control.
−Removed: Further, in response to the persistent capital outflow in the PRC and RMB’s depreciation against the U.S.
−Removed: 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.
−Removed: Such measures were relaxed in mid-2017 with the slowdown of the capital outflow and stabilizing of the RMB.
−Removed: 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.
−Removed: 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.
+Added: However, conversion of RMB to other currencies are permitted for the purpose of dividends according to the PRC’s regulations on foreign exchange administration.
+Added: Notwithstanding the foregoing, 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.
−Removed: 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
−Removed: PRC entities provided that the recipient can demonstrate it is a Hong Kong tax resident and it is the beneficial owner of the dividends.
+Added: 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.
−Removed: 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.
+Added: Specifically, it expressly excludes an agent or a designated payee from being considered as a “beneficial owner.” We own the PRC subsidiaries through BeiGene (Hong Kong) Co., Limited (“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.
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Our operations in the PRC are governed by PRC laws and regulations.
−Removed: 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.
+Added: 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, clinical trial applications, 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.
1 unchanged sentence
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.
−Removed: 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.
+Added: 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 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.
1 unchanged sentence
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.
−Removed: On February 17, 2023, the CSRC released the Overseas Listing Trial Measures and five relevant guidelines, which will take effect from March 31, 2023.
+Added: On February 17, 2023, the CSRC released the Overseas Listing Trial Measures and five relevant guidelines, which took effect 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”.
−Removed: 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.
+Added: 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 NASDAQ 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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
−Removed: 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
−Removed: processes and funding arrangements.
−Removed: Our management reviews and monitors our cash flow forecast and working capital needs of our subsidiaries on a regular basis.
+Added: 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.
+Added: Our management reviews and monitors our cash and working capital needs and external debt repayment and borrowing needs, of our subsidiaries on a regular basis.
In addition, capital contributions and intercompany loan arrangements are subject to local jurisdiction and banking regulations.
−Removed: In this regard, we have not faced difficulties or limitations in our ability to transfer cash between subsidiaries in any of our operating jurisdictions.
−Removed: 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.
−Removed: Cash is maintained by BeiGene, Ltd.
−Removed: 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.
−Removed: In addition, cash may be used by BeiGene, Ltd.
−Removed: 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.
−Removed: Cash is transferred between subsidiaries in the form of capital contributions or through intercompany advances or loans, as follows:
−Removed: • 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.
+Added: BeiGene, Ltd.
+Added: and its subsidiaries hold cash in demand deposits, time deposits and money market funds for the operating needs of each entity, including from intercompany transactions.
+Added: As needed, cash to fund both short-term operating needs (such as investments in inventory or sales marketing capabilities) and long-term investment needs (such as for property, plant and equipment) can be transferred from BeiGene Ltd.
+Added: or between subsidiaries to supply additional liquidity using capital contributions, intercompany advances or loans, as follows:
+Added: • Cash may be transferred between BeiGene HK and its operating subsidiaries in mainland China through intercompany loans and capital contributions.
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, 2022 and December 31, 2023.
For the year ended December 31, 2022 and December 31, 2023, the amount of cash transferred between BeiGene HK and its subsidiaries in mainland China was $351 million and $295 million, respectively.
−Removed: • Cash may be transferred between BeiGene UK and/or BeiGene Switzerland and their respective operating subsidiaries through intercompany fund advances and capital contributions.
+Added: • Cash may be transferred between BeiGene UK, Ltd.
+Added: (“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.
−Removed: 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.
+Added: Cash generated from BeiGene UK and BeiGene Switzerland may be 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 December 31, 2022 and December 31, 2023.
For the year ended December 31, 2022 and December 31, 2023, the amount of cash transferred between BeiGene UK to its respective subsidiaries was $4 million and $270 million, respectively.
−Removed: 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.
+Added: For the years ended December 31, 2022 and December 31, 2023, the amount of cash transferred between BeiGene Switzerland to its respective subsidiaries was $65 million and nil, respectively.
Human Capital Resources
We are committed to attracting and retaining exceptional, passionate people to work with a clear purpose:
−Removed: creating impactful, affordable and accessible medicines to help more patients around the world to live better.
−Removed: To this end, we support a team-oriented culture based on excellence that allows all colleagues to feel valued and challenged.
−Removed: We provide opportunities for employees to grow and develop in their careers, supported by competitive compensation, benefits and health and wellness programs, and by programs that build connections among our employees worldwide.
+Added: creating impactful, affordable and accessible medicines to help more patients around the world live better.
+Added: To this end, we provide opportunities for employees to grow and develop in their careers, supported by competitive compensation, benefits, health and wellness programs, and by programs that build connections among our employees worldwide.
We believe that the success of our business is fundamentally connected to the well-being of our employees.
−Removed: Accordingly, we are committed to their health, safety and wellness.
−Removed: We offer our employees and their families innovative, flexible and convenient health and wellness programs, including benefits that confer peace of mind around events that may require time away from work or impact their financial well-being;
−Removed: that support their physical and mental health with tools and resources to help them improve or maintain their health status and encourage healthy behaviors;
−Removed: and that offer choice where possible so they can customize benefits to meet their needs and the needs of their families.
−Removed: In order to support our employees during the COVID-19 pandemic, we implemented significant changes that we determined were in the best interest of our employees, as well as the communities in which we operate, and which comply with government regulations.
−Removed: This included initiating a number of mental-health programs and offering supplemental resources that are available to all of our employees, having our employees work from home and implementing additional safety measures for employees continuing critical work at our offices or in the field, as well as encouraging employees to adhere to preventative measures recommended by the World Health Organization, U.S.
−Removed: Centers for Disease Control and Prevention, and similar public health authorities.
+Added: Hence, we take a holistic view of well-being – one that considers financial, physical, and social-emotional health – we are working to cultivate a community and culture where our colleagues can find balance both professionally and personally.
+Added: Accordingly, we offer our employees and their families innovative, flexible and convenient health and wellness programs, that are tailored to the region of the world where they work.
+Added: Our competitive compensation and benefits programs help meet the needs of our employees.
+Added: In addition to base salaries, these programs include potential annual discretionary bonuses, equity awards, a 401(k) plan in the U.S.
+Added: and pension plans in other jurisdictions, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and flexible work schedules, among others.
+Added: In addition to our broad-based equity award programs, we have used equity-based grants with vesting conditions to facilitate retention of key personnel.
+Added: In addition to compensation and benefits, we provide our employees opportunities for growth through challenging job assignments, performance management and training opportunities.
+Added: We seek to remain competitive in our compensation and benefits by routinely benchmarking against industry peers.
Our worldwide teams are united by a common mission.
1 unchanged sentence
Our management team routinely makes themselves available to all employees, including in regular town hall events that encourage open dialogue.
−Removed: Fostering a culture of accountability and compliance is also central to our human resource management.
−Removed: All of our employees complete trainings
−Removed: on applicable corporate policies including our global Code of Conduct;
+Added: Fostering a culture of accountability and compliance is also important, and all of our employees complete trainings on applicable corporate policies including our Global Code of Conduct;
Harassment, Discrimination, and Retaliation Policy;
2 unchanged sentences
and Anti-Corruption Policy.
−Removed: We strive to provide competitive compensation and benefits programs to help meet the needs of our employees.
−Removed: In addition to base salaries, these programs include potential annual discretionary bonuses, equity awards, a 401(k) plan in the United States and pension plans in other jurisdictions, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and flexible work schedules, among others.
−Removed: In addition to our broad-based equity award programs, we have used targeted equity-based grants with vesting conditions to facilitate retention of personnel.
−Removed: In addition to compensation and benefits, we provide our employees opportunities for growth through challenging job assignments, performance management and training opportunities.
−Removed: We seek to remain competitive in our compensation and benefits by routinely benchmarking against industry peers.
−Removed: As part of our mission to create the innovative medicines to serve the patients, we continue to advance our environmental, social and governance ("ESG") efforts, including enhancing the diversity and inclusiveness of our workplace.
−Removed: We believe that diversity of backgrounds and ideas inspires creativity and helps us create the innovative medicines patients need.
−Removed: We appreciate one another’s differences and strengths, and are proud to be an equal opportunity employer.
+Added: At BeiGene, empowering our people begins with our culture and values:
+Added: Bold Ingenuity, Collaborative Spirit, Driving Excellence, and most importantly, Patients First.
+Added: As a global entity with many remote workers, we have been able to build a diverse team of talented professionals, regardless of their location.
+Added: As a global organization, we are comprised of employees at various life stages, of multiple backgrounds, and from diverse cultures, where everyone can share their ideas and perspectives.
+Added: We celebrate our differences and value diversity and inclusion in the workplace.
+Added: We believe that diversity of backgrounds and ideas inspire creativity and help us create the innovative medicines patients need.
+Added: We are proud to be an equal opportunity employer.
BeiGene does not discriminate on the basis of race, religion, color, sex, gender identity, sexual orientation, age, non-disqualifying physical or mental disability, national origin, veteran status or any other basis covered by applicable law.
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We maintain an inclusive culture where all voices are welcomed, heard, and respected.
−Removed: As of January 31, 2023, we had approximately 9,200 full-time employees worldwide, with approximately 1,300 employees in the United States and approximately 7,900 employees outside of the United States.
+Added: As of February 14, 2024, we had approximately 10,600 full-time employees worldwide, across five continents, with approximately 1,600 employees in the U.S.
+Added: and the balance outside of the U.S.
We have also engaged and may continue to engage independent contractors to assist us with our operations.
1 unchanged sentence
We have never experienced any employment-related work stoppages, we also track voluntary and involuntary turnover rates and we consider our relations with our employees to be good.
−Removed: Environmental, Social and Governance Strategy
−Removed: BeiGene’s mission is to expand access to high-quality, affordable medicines to billions more people globally.
−Removed: We are driven to deliver affordable medicines to all and create a more equitable and sustainable world for our patients, employees, and our communities.
−Removed: In 2022, we announced our global ESG strategy, Change Is the Cure , which guides our efforts across five focus areas:
−Removed: advancing global health, empowering people, innovating sustainably, supporting communities, and operating responsibly.
−Removed: Within each focus area, we have identified two strategic priorities against which we have set concrete targets.
−Removed: 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.
−Removed: While we are at the start of our ESG journey, we are proud of the progress we have made to date.
+Added: Responsible Business & Sustainability Strategy
+Added: In 2022, we announced our global strategy, Change Is the Cure , which guides our efforts across five focus areas:
+Added: advancing global health, empowering our people, innovating sustainably, supporting communities, and operating responsibly.
+Added: Within each focus area, we have identified key strategic priorities against which we have set concrete targets.
+Added: We report our progress against our targets in late April of each year.
+Added: While we are at the start of our journey, we are proud of the progress we have made to date.
We joined the United Nations Global Compact in 2022 and have aligned our efforts with UN Sustainable Development Goals.
−Removed: In 2022, we announced new measures to understand and further mitigate our climate impacts.
−Removed: 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.
+Added: In 2023, we also announced a collaboration with the Max Foundation, a global nonprofit organization dedicated to accelerating health equity by delivering medication, technology, and supportive services to patients worldwide, BeiGene, and the BeiGene Foundation, a nonprofit charitable foundation, to provide access to BRUKINSA for the treatment of adult patients with CLL in 29 low- and middle-income countries over the next three years.
+Added: This collaboration advances each organization’s focus on patient access by combining the Max Foundation’s expertise and infrastructure with a donated product from BeiGene, and a grant from the BeiGene Foundation.
We believe that our people are critical to our success and, as a global company, we know that sharing diverse ideas and perspectives spurs greater innovation and enhances our ability to deliver results.
Our culture celebrates and encourages the voices of all our employees and promotes a respectful, collaborative environment.
+Added: Our Diversity, Equity, Inclusion & Belonging strategy, Belong@BeiGene, is centered on bringing diverse voices to the forefront of our work and embedding inclusion in all aspects of BeiGene’s operations.
+Added: Our strategy encompasses three areas:
+Added: Workforce (our people), Workplace (our culture) and Marketplace (our communities).
In 2020, we formed the Inclusion, Diversity, Equity, and Awareness (“IDEA”) Council to provide a forum for U.S.
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Introduced first in the U.S., the IDEA Council is now global, with members in geographies including Canada, Europe, China, and Australia.
−Removed: In 2022, we completed a three-year diversity, equity, inclusion and belonging strategy.
−Removed: Details will be shared in our 2022 ESG Report.
−Removed: In addition to directly supporting patients through the delivery of cutting-edge therapies, we strive to support our communities through research, education, and sponsorships.
−Removed: We support patient advocacy organizations, charitable foundations, and hospitals through cash and in-kind donations.
−Removed: More details about our ESG strategy, goals and progress to date will be available in our 2022 ESG Report, which will be developed with reference to the Global Reporting Initiative Standards and published in late April 2023.
−Removed: Our previous ESG Reports can be found online at:
−Removed: https://hkexir.beigene.com/governance/esg-report/.
+Added: In 2022, we completed a three-year diversity, equity, inclusion and belonging strategy, and in 2023, an Executive Director, Diversity and Global Health Equity was brought on board to lead our effort in this area.
+Added: In addition to directly supporting patients through the delivery of cutting-edge therapies, we strive to support the communities in which we live and work.
+Added: In 2023, the BeiGene Foundation was established as an independent 501(c)(3) organization to provide grants to charitable organizations aligned with the Foundation’s mission.
+Added: Related to volunteerism, we expanded our employee volunteer paid time-off policy to colleagues worldwide and in July 2023, Be the Change, a global employee volunteer platform, was officially launched.
+Added: This platform enables colleagues to learn about local and national community partnerships, create or register for volunteer opportunities, and record volunteer hours.
+Added: More details about our Responsible Business & Sustainability strategy, goals and progress to date will be available in our 2023 Responsible Business & Sustainability Report, which will be published in late April 2024.
+Added: Our previous progress reports can be found on our corporate website at www.beigene.com.
Financial Information
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Corporate Information
−Removed: We are an exempted company incorporated in the Cayman Islands with limited liability on October 28, 2010.
+Added: We are an exempted company incorporated on October 28, 2010 in the Cayman Islands with limited liability.
Any company that is registered in the Cayman Islands but conducts business mainly outside of the Cayman Islands may apply to be registered as an exempted company.
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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.