DXP-593

点击蓝字GBIHealth关注我们SUBSCRIBE to us近期，随着国内疫情防控政策的调整，各类新冠药物再次成为大众关注的焦点，前有3天内4款国产新冠疫苗获准紧急使用，后有石药、歌礼、广生堂等旗下小分子口服药物取得最新进展。此外，昨日晚间，据界面新闻，多个互联网平台已经开始、或即将放开销售辉瑞Paxlovid以及真实生物阿兹夫定，定价分别为2980元/盒和330元/瓶（1mg*35片）。国内新冠赛道持续升温，“入局者”们的激烈竞速一触即发。布局新冠赛道的国内企业有哪些？疫苗/治疗类药物获批情况和研发进展如何？哪些在研产品值得重点关注？疫苗：13款国产可选择，近20款临床中根据世界卫生组织（WHO）数据，截至2022年12月6日，全球在研新冠疫苗175个，处于临床前阶段的199个。处于临床阶段的疫苗中，蛋白亚单位（Protein subunit）、RNA类疫苗占比较高。聚焦国内市场，目前布局新冠疫苗领域的企业超过20家，产品技术路径主要集中在灭活疫苗、腺病毒载体疫苗、mRNA疫苗、重组蛋白疫苗等。来源：https://www.who.int/累计13款国产疫苗可选择据GBI统计，目前国内已经有13款新冠疫苗获得国家药监局批准附条件上市或纳入紧急使用，包含11个注射式、1个吸入式以及1个鼻喷式疫苗（详见表1）。表1. 国内获批上市或纳入紧急使用的新冠疫苗*首次获批日期不计军队特批时间来源：GBI 整理其中，国药中生北京公司新冠灭活疫苗、科兴中维新冠灭活疫苗以及康希诺重组新冠病毒疫苗（5型腺病毒载体）被列入WHO紧急使用清单（EUL）。科兴中维克尔来福/CoronaVac是WHO EUL中唯一被推荐在3至4岁儿童中使用的新冠疫苗。13个疫苗中有8个是纳入紧急使用。其中神州细胞SCTV01C、威斯克生物威克欣、三叶草生物SCB-2019（CpG 1018/铝佐剂），以及万泰生物鼻喷流感病毒载体新冠肺炎疫苗在2022年12月4至6号三天内，接连在中国被纳入紧急使用。GBI既往报道，SCTV01C是神州细胞针对新冠病毒变异快、以原始株为基础的国内外第一代疫苗对变异株中和抗体滴度和保护率下降等问题自主研发的新一代二价变异株重组蛋白疫苗，临床上拟用于预防新型冠状病毒感染所致疾病；威克欣是中国首个获批紧急使用的、由昆虫细胞技术平台生产的重组蛋白新型冠状病毒疫苗；三叶草SCB-2019（CpG 1018/铝佐剂）在全球II/III期SPECTRA研究最新数据显示可降低84%家庭传播风险；万泰生物鼻喷流感病毒载体新冠疫苗采用鼻腔喷雾剂给药，其模仿呼吸道病毒的自然感染途径，以激活局部和全身免疫反应，在病毒进入人体后更快地发挥作用。另外值得关注的是，上述大部分产品都在海外多国获得紧急使用授权或处于临床后期阶段。近20款I-III期临床，mRNA疫苗受瞩目除了已经获批上市或纳入紧急使用的疫苗外，据GBI统计，目前还有近20个国产疫苗产品处于临床研发阶段（详见表2）。表2. 国产在研新冠新苗情况来源：GBI 整理在临床阶段的产品中，mRNA疫苗数量过半。目前中国大陆暂无mRNA疫苗获批上市，国内聚焦此领域的企业中，有十余家旗下药物进入临床阶段，其中进展较快的有艾博生物/沃森生物/军事科学院的ARCoV，处于国内III期阶段；艾美疫苗/丽凡达的LVRNA009和云顶新耀/Providence的PTX-COVID19-B分别在国内和海外推进到临床II期；石药集团的SYS6006的I、II期临床试验及序贯加强免疫的临床研究报告均已上交CDE；复星医药/BioNTech的复必泰（BNT162b2）已在港澳台三地获紧急使用授权，其在中国内地的II期临床试验结束，上市审批工作仍在积极沟通中。此外，还有瑞科生物、斯微生物、康希诺等企业旗下mRNA疫苗处于临床早期阶段。小分子药物：1款国产获批上市，20+布局临床关注新冠小分子口服药物，目前全球两大“领头羊”为默沙东和辉瑞。2021年11月，默沙东的莫努匹拉韦（Molnupiravir）在英国获批上市，成为全球首个获批用于治疗成人轻度至中度COVID-19的口服抗病毒药物。据GBI全球药品价格数据，莫努匹拉韦的售价为700美元/盒，即18美元/片。辉瑞旗下新冠口服药Paxlovid（奈玛特韦片/利托那韦片）已在包括中国在内的约70个市场获批上市、有条件批准上市，或紧急使用授权。聚焦国内市场，首个获批的国产新冠小分子药物为真实生物旗下阿兹夫定。该产品是我国自主研发的口服小分子药物，分别于2021年7月和2022年7月获批HIV和COVID-19适应证，复星医药拥有该药部分区域的独家商业权益。2022年8月，国家卫健委和中医药局发布通知，将阿兹夫定片纳入《新型冠状病毒肺炎诊疗方案（第九版）》。相比于新冠中和抗体，小分子口服药具有生产成本低、储运条件易满足、服用方便、病人顺应性好等优势。诸多优点与广阔的市场空间也引得国内企业积极入局，加速推进海内外研发进程（详见表3）。表3. 国内企业在研/已上市新冠小分子药物来源：GBI 整理在研药物中，进展较快的为君实生物/中科院/旺山旺水的VV116，目前已在国内完成一项III期临试，多项国际多中心的III期临试进行中；前沿生物的FB2001注射剂和雾化吸入剂分别在海外和国内推进至II/III期；开拓药业的普克鲁胺正在进行用于轻中症非住院新冠患者的III期全球多中心临床试验和一项用于重症住院新冠患者的III期全球多中心临床试验；众生药业的RAY1216已启动新冠治疗III期临试。此外，海创药业、埃格林医药、远大医药、科兴制药、泽璟制药旗下新冠小分子药物均处于临床II期。另外还有先声药业、广生堂、石药集团、歌礼制药等企业在加速推进相关药物的研发进程。抗体类：1款国产上市，I/II期临床居多关注新冠抗体类药物，目前国内只有腾盛博药新冠病毒中和抗体联合治疗药物安巴韦单抗/罗米司韦单抗（BRII-196/BRII-198）获批上市，其余药物大多处于国内外临床早期阶段（详见表4）。表4. 国内企业在研/已上市新冠抗体类药物来源：GBI 整理GBI既往报道，礼来制药此前已获得君实生物埃特司韦单抗（JS016）在大中华区以外地区的权益，2021年埃特司韦单抗和巴尼韦单抗联合的双抗体疗法在全球超过15个国家和地区获得紧急使用授权，用于治疗COVID-19患者。其余进展较快的新冠中和抗体包括：神州细胞SCTA01、丹序生物/百济神州的DXP-604和DXP-593、迈威生物9MW3311、绿叶制药LY-CovMab、信达生物IBI314、济明可信JMB2002、以及舒泰神BDB-001。新冠抗原测试剂：累计42款获批上市除了疫苗与治疗类药物外，新冠抗原测试剂也在加速获批中。12月8日，国家药监局发布《关于延长新冠病毒抗原检测试剂注册证有效期的公告》，将已获准注册的新冠病毒抗原检测试剂的注册证有效期，在原有效期基础上延长6个月，以切实保障相关产品市场供应。12月11日，国家药监局宣布批准佰奥达生物科技（武汉）股份有限公司、基蛋生物科技股份有限公司、泰普生物科学（中国）有限公司、中山生物工程有限公司的新冠抗原检测试剂上市。12月12日，郑州安图生物工程股份有限公司、厦门为正生物科技股份有限公司的新冠抗原检测试剂获批上市。据GBI DEVINT医疗器械数据库，目前我国已上市的新冠抗原检测产品多达42款。随着疫情防控政策的不断调整，未来对于新冠预防和治疗类药物的需求或将大大增加。我们期待研发进展较快的药物早日获批上市，也将持续追踪其他“入局者”们以及旗下药物的最新进展。小编温馨提示近期全国疫情多点频发，大家一定要增强自身免疫力、注意个人防护哦～让我们共同期待来年疫情消散之时，在春暖花开中共赴山海！重磅推荐*点击图片了解详情《高值创新药医保报销风险管理——国际经验：创新型支付协议从概念到案例》报告由清华大学医院管理研究院教授兼研究员、GBI首席顾问陈怡博士撰写，报告在汇总相关国际文献基础上，梳理了创新型市场准入协议（Market Access Agreement, MAA）的发展背景、协议类别、实施条件、评估标准、案例和发展趋势，旨在帮助行业同仁系统地认识国际实践经验，并对未来如何建立适合我国的高值药品准入支付方式解决思路带来启示与思考。滑动查看报告目录扫描二维码或点击“阅读原文”解锁完整版报告精彩内容。点击 阅读原文 获取完整版报告

Nov. 4, 2021 20:05 UTC Recorded product revenue of $192.5 million for the third quarter, representing a 111% increase from $91.1 million in the prior year period Received approvals for BRUKINSA® in two new indications in the U.S. and approvals in six other markets Submitted first biologics license application (BLA) in the U.S. for tislelizumab in collaboration with Novartis for patients with advanced or metastatic esophageal squamous cell carcinoma following prior systemic therapy CAMBRIDGE, Mass. & BEIJING--(BUSINESS WIRE)-- BeiGene Co.,Ltd (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, today reported recent business highlights, anticipated upcoming milestones, and financial results for the third quarter and nine months ended September 30, 2021. “We remain focused on translating science into highly impactful medicines and making these medicines more affordable and accessible to many more people with cancer around the world,” said John V. Oyler, Co-Founder, Chairman and Chief Executive Officer of BeiGene. “In the third quarter we had two new indications approved for BRUKINSA in the United States, and recent BRUKINSA approvals in Australia, Singapore, Brazil, Russia, and Chile as well as a positive CHMP opinion for our first BRUKINSA filing in Europe. Tislelizumab’s BLA for esophageal squamous cell carcinoma (ESCC) has been accepted for review by the FDA, which is the first filing for our internally developed anti-PD-1 medicine outside of China and an important achievement in our collaboration with Novartis. This is one of many global tislelizumab studies that comprise a comprehensive PD-1 program that has enrolled over 5,600 patients in more than 30 countries and regions and includes over 1,700 patients from outside of China. We also continued to expand and strengthen our strategic competitive advantages that we feel are critical to transform the industry and bring innovative and accessible medicines to billions more people around the world. These include research, predominantly CRO-free global clinical development, global commercial infrastructure, and internal manufacturing capabilities.” Recent Business Highlights and Upcoming Milestones Commercial Operations Product sales increased 111% in the third quarter of 2021 compared to the prior year period, primarily due to increased sales of our internally developed products and in-licensed products from Amgen; Global sales of BRUKINSA totaled $65.8 million in the third quarter, representing a 320% increase compared to the prior year period; U.S. sales of BRUKINSA totaled $33.7 million in the third quarter compared to $5.7 million in the comparable prior year period. U.S. sales continued to accelerate in the quarter, driven by continued uptake in mantle cell lymphoma (MCL) and the recent FDA approvals in Waldenström’s macroglobulinemia (WM) and marginal zone lymphoma (MZL). BRUKINSA sales in China totaled $32.1 million in the third quarter, representing growth of 223% compared to the prior year period, driven by a significant increase in all approved indications, including chronic lymphocytic leukemia (CLL); Sales of tislelizumab in China totaled $77.0 million in the third quarter, representing a 54% increase compared to the prior year period. In the third quarter, new patient demand from broader reimbursement and further expansion of our salesforce and hospital listings continued to drive increased market penetration and market share for tislelizumab; The commercial organization in China continued to demonstrate its ability to bring new products to market, launching the second product from the Amgen collaboration, BLINCYTO® (blinatumomab), which contributed $5.0 million of sales in the third quarter. Two additional new products are expected to be approved or launched by the end of the year; and We are preparing for the upcoming National Reimbursement Drug List (NRDL) negotiation in China for our eligible medicines, including tislelizumab in first-line non-squamous non-small cell lung cancer (NSCLC), first-line squamous NSCLC and second- or third-line hepatocellular carcinoma (HCC), BRUKINSA in WM, and pamiparib in 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. The NRDL negotiations are anticipated to be completed in the fourth quarter of 2021. Development Programs BRUKINSA® (zanubrutinib), a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to maximize BTK occupancy and minimize off-target effects, approved in the U.S., China, Canada, Australia, and other international markets in selected indications and under development for additional approvals globally. Received FDA approvals in two new indications, including full approval for the treatment of adult patients with WM, and accelerated approval for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen; Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), recommending approval for the treatment of adult patients with WM who have received at least one prior therapy or first-line treatment for patients unsuitable for chemo-immunotherapy; Was granted a cohort Temporary Authorization for Use (cATU), an early access program, for patients with WM by the French National Agency for Medicines and Health Products Safety (ANSM); Received acceptance of the marketing authorization application (MAA) from Swissmedic and the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for patients with WM; Received approval in Australia for the treatment of adult patients with MCL who have received at least one prior therapy and for patients with WM who have received at least one prior therapy or in first line treatment for patients unsuitable for chemo-immunotherapy; and Continued to advance BRUKINSA in new markets. BRUKINSA is now approved in Australia, Russia, Singapore, Brazil, Chile, Israel, and UAE for patients with MCL who have received at least one prior therapy. There currently are more than 20 marketing authorization applications in multiple indications under review around the world. Expected Milestones for BRUKINSA Receive EMA approval for treating adult patients with WM who have received at least one prior therapy or first-line treatment for patients unsuitable for chemo-immunotherapy in 2021; Report results from the Phase 3 SEQUOIA trial (NCT03336333) comparing BRUKINSA with bendamustine plus rituximab in patients with treatment-naïve CLL or small lymphocytic lymphoma (SLL); and early results from Arm D in patients with del(17p) in combination with venetoclax in two oral presentations at the 63rd American Society of Hematology (ASH) Annual Meeting taking place December 11-14, 2021; Continue to discuss Phase 3 clinical trial results in CLL with regulatory agencies in the U.S., Europe, and other countries; Report additional results from the Phase 3 ALPINE trial (NCT03734016) in 2022; and Continue to expand BRUKINSA’s registration program globally in new geographies and indications, including potential additional approvals in 2021 and the first half of 2022 for certain patients with MCL in APAC, the Middle East and South America. Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages; approved in China in selected indications and under development for additional approvals globally. Received acceptance by the FDA of a BLA for tislelizumab in collaboration with Novartis as a treatment for patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy. The Prescription Drug User Fee Act (PDUFA) target action date is July 12, 2022; Received acceptance by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) of a supplemental BLA (sBLA) in combination with chemotherapy as a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (NPC); Received approval from the NMPA in a new indication, for front-line squamous NSCLC with nab-paclitaxel and carboplatin; and Reported data at the European Society for Medical Oncology (ESMO) Congress 2021 including: – RATIONALE 304 (NCT03663205): Tislelizumab plus chemotherapy vs. chemotherapy alone as first-line treatment for non-squamous NSCLC in patients who are smokers vs. non-smokers; and – RATIONALE 307 (NCT03594747): Tislelizumab plus chemotherapy vs. chemotherapy alone as first-line treatment for advanced squamous NSCLC in patients who were smokers vs. non-smokers. Expected Milestones for Tislelizumab Receive approvals in China for the four sBLAs currently under review in first-line NPC, second- or third-line NSCLC, second-line ESCC, and second- or third-line MSI-High solid tumors in 2022. Pamiparib, a selective small molecule inhibitor of PARP1 and PARP2 conditionally approved in China for the treatment of patients with germline BRCA mutation-associated advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy. Expected Milestones for Pamiparib Report topline results from the Phase 3 trial (NCT03519230) of pamiparib as a maintenance treatment in patients with platinum-sensitive recurrent ovarian cancer, in 2021 or the first half of 2022. Ociperlimab (BGB-A1217), an investigational anti-TIGIT monoclonal antibody with competent Fc function Initiated patient enrollment in the Phase 2 AdvanTIG-206 trial (NCT04948697) of ociperlimab in combination with tislelizumab plus Bio-Thera’s POBEVCY® (BAT1706), a biosimilar to bevacizumab (Avastin®), as first-line treatment in patients with advanced HCC. Expected Milestones for ociperlimab Initiate patient enrollment in the global Phase 2 AdvanTIG-205 trial (NCT05014815) in frontline stage IV NSCLC, in 2021. BGB-11417, an investigational BCL-2 inhibitor Initiated patient enrollment in a Phase 1 trial (NCT04973605) in patients with multiple myeloma with t (11;14) translocation, in 2021. Expected Milestones for BGB-11417 Begin patient enrollment in pivotal trials, in 2022. Early-Stage Programs Continued to advance our early-stage clinical pipeline of internally-developed product candidates at dose escalation stage, including BGB-A445 (an investigational non-ligand competing OX40 monoclonal antibody as monotherapy or in combination with tislelizumab in solid tumors), BGB-15025 (an investigational hematopoietic progenitor kinase 1 (HPK1) inhibitor as monotherapy or in combination with tislelizumab in solid tumors), BGB-10188 (an investigational PI3Kδ inhibitor as monotherapy or in combination with BRUKINSA in hematology malignancies, or in combination with tislelizumab in solid tumors); BGB-16673 (an investigational Chimeric Degradation Activating Compound, or CDAC, targeting BTK) received investigational new drug (IND) clearance and permission to proceed from the FDA. Patient dosing in the first Phase 1 trial (NCT05006716) in patients with B-cell malignancies is expected to begin in 2021; and BGB-A425 (an investigational TIM3 monoclonal antibody) study advanced to the Phase 2 portion of the Phase 1/2 trial (NCT03744468) in combination with tislelizumab. Collaboration with Amgen Secured approval by the Hainan BoAo government for early access to LUMAKRAS® (sotorasib, a KRAS G12C inhibitor) in designated hospitals in the province. Other Collaboration Programs Announced that the NMPA granted QARZIBA® (dinutuximab beta) conditional approval 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. QARZIBA is a targeted immunotherapy licensed by EUSA Pharma to BeiGene in mainland China; Received notification by BMS-Celgene of its intent to terminate a license and supply agreement with respect to ABRAXANE® (nanoparticle albumin-bound paclitaxel) in China. BeiGene contests this action, as it believes that the reasons provided by BMS-Celgene are not valid bases for terminating the agreement with respect to ABRAXANE. Arbitration proceedings are ongoing between the parties regarding BMS-Celgene’s failure to ensure the continuity and adequacy of its supply of ABRAXANE under the agreement in accordance with Good Manufacturing Practices (GMP); and Received results from the Phase 2 trial (NCT04551898) evaluating investigational SARS-CoV-2 neutralizing antibody BGB-DXP593 in patients with mild to moderate COVID-19, licensed from Singlomics outside of China. The trial did not meet the primary efficacy endpoint of viral load change in nasopharyngeal swabs at Day 8. The license rights of the two Singlomics candidates (DXP593 and DXP604) outside of the U.S. and the development rights of the candidates in the U.S. have been returned to Singlomics under a reversion agreement signed by the parties, with BeiGene retaining U.S. commercial rights. Sitravatinib, an investigational tyrosine kinase inhibitor of receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, MER), split family receptors (VEGFR2, KIT) and RET, licensed from Mirati Therapeutics Inc. (Mirati), in Asia (excluding Japan), Australia, and New Zealand. Reported data at the European Society for Medical Oncology (ESMO) Congress 2021: − Sitravatinib + tislelizumab in patients with anti-PD-(L)1 refractory/resistant metastatic NSCLC (NCT03666143); and − Sitravatinib + tislelizumab in patients with metastatic NSCLC (NCT03666143). Zanidatamab, (ZW25) an investigational bispecific HER2 antibody targeting HER2 in late-stage clinical development with Zymeworks, Inc. Expected Milestones for Zanidatamab Initiate a Phase 3 clinical trial in first-line HER2+ gastric cancer, in 2021. Manufacturing Operations Continued efforts to secure geographically diverse manufacturing and supply chain redundancy with the previously announced plans to build a new commercial-stage manufacturing and clinical R&D campus at Princeton West Innovation Park in Hopewell, New Jersey. The acquisition of the property is expected to close in 2021; Continued construction on the new small molecule manufacturing campus in Suzhou, China. Phase 1 of construction will bring over 50,000 square meters and 600M solid preparation capacity and is expected to be completed in 2023. Once completed, the total production capacity is expected to increase BeiGene's small molecule manufacturing capability in China by up to six times the current capacity; and Two additional 2,000L bioreactors at Boehringer Ingelheim’s facility are available to support commercial production of tislelizumab’s expanding indications in China. This is in addition to BeiGene’s state-of-the-art biologics facility in Guangzhou, China, which currently is approved for 8,000 liters of biologics capacity with an additional phase of construction expected to bring total capacity to 64,000 liters, and to be completed by the end of 2022. COVID-19 Impact and Response The Company expects that the worldwide health crisis of COVID-19 will continue to have a negative impact on its operations, including commercial sales, regulatory interactions, inspections, filings, and clinical trial recruitment, participation, and data read outs. There remains uncertainty regarding the future impact of the pandemic globally. The Company is striving to minimize delays and disruptions, and continues to execute on its commercial, regulatory, manufacturing, and clinical development goals globally. Corporate Developments Listing of the Company’s ordinary shares on the Science and Technology Innovation Board (STAR Market) of the Shanghai Stock Exchange is expected to be completed in 2021, subject to market conditions and additional regulatory approvals; and Received inclusion in several FTSE Russell indices, including: the FTSE Global Equity Index Large Cap; the FTSE All-World (LM); the FTSE All-Cap (LMS); and the FTSE Total-Cap (LMSµ). In addition, BeiGene was included in the FTSE Developed ESG Low Carbon Select Index, and the FTSE Asia ex Japan ESG Low Carbon Select Index, reflecting the Company’s commitment to sustainability. Third Quarter 2021 Financial Results Cash, Cash Equivalents, Restricted Cash, and Short-Term Investments were $3.9 billion as of September 30, 2021, compared to $4.4 billion as of June 30, 2021, and $4.7 billion as of December 31, 2020. In the three months ended September 30, 2021, cash used in operating activities was $495.7 million, primarily due to our net loss of $413.9 million and a $89.4 million increase in our net operating assets and liabilities, offset by non-cash charges of $7.5 million; capital expenditures were $67.0 million; and cash provided by financing activities was $109.2 million, consisting primarily of $50 million in proceeds from the sale of shares to Amgen, as well as the exercise of employee share options. Revenue for the three months ended September 30, 2021 was $206.4 million, compared to $91.1 million in the same period of 2020. Product revenue totaled $192.5 million for the three months ended September 30, 2021, compared to $91.1 million in the same period of 2020, including: – Sales of tislelizumab in China of $77.0 million, compared to $49.9 million in the prior year period; – Sales of BRUKINSA of $65.8 million, compared to $15.7 million in the prior year period; – Sales of XGEVA® (denosumab), the first product transferred to BeiGene from the Amgen collaboration, in China of $15.7 million, compared to $3.1 million in the prior year period. BeiGene commenced sales and marketing in China in July 2020; Collaboration revenue for the three months ended September 30, 2021 was $14.0 million, resulting from the partial recognition of previously deferred revenue associated with the upfront payment received from Novartis in the first quarter of 2021. There was no collaboration revenue in the prior year period. Expenses for the three months ended September 30, 2021 were $668.8 million, compared to $531.2 million in the same period of 2020. Cost of Sales for the three months ended September 30, 2021 were $47.4 million, compared to $21.1 million in the same period of 2020. Cost of sales increased primarily due to increased product sales of tislelizumab, BRUKINSA, and XGEVA. R&D Expenses for the three months ended September 30, 2021 were $351.9 million, compared to $349.1 million in the same period of 2020. The increase in R&D expenses was primarily attributable to increases in headcount and external costs related to our investment in discovery and development activities, including our continued efforts to internalize research and clinical trial activities, partially offset by decreased spending on clinical trials related to BRUKINSA, as well as decreased expense related to upfront fees related to in-process R&D. Additionally, R&D-related share-based compensation expense was $31.7 million for the three months ended September 30, 2021, compared to $25.4 million for the same period of 2020. SG&A Expenses for the three months ended September 30, 2021 were $269.2 million, compared to $160.8 million in the same period of 2020. The increase in SG&A expenses was primarily attributable to increased headcount and increased external expenses related to the growth of our global commercial organization, as we continued to build our worldwide footprint. SG&A-related share-based compensation expense was $35.4 million for the three months ended September 30, 2021, compared to $24.9 million for the same period of 2020. Net Loss for the three months ended September 30, 2021 was $413.9 million, or $0.34 per share, and $4.46 per American Depositary Share (ADS), compared to $425.2 million, or $0.37 per share, and $4.81 per ADS in the same period of 2020. Financial Summary Select Condensed Consolidated Balance Sheet Data (U.S. GAAP) (Amounts in thousands of U.S. Dollars) As of September 30, December 31, 2021 2020 (unaudited) (audited) Assets: Cash, cash equivalents, restricted cash and short-term investments $ 3,923,313 $ 4,658,730 Accounts receivable, net 129,584 60,403 Working capital 3,128,400 3,885,491 Property and equipment, net 450,788 357,686 Total assets 5,286,334 5,600,757 Liabilities and equity: Accounts payable 206,203 231,957 Accrued expenses and other payables 389,874 346,144 Deferred revenue 124,898 — R&D cost share liability 420,001 502,848 Debt 643,278 518,652 Total liabilities 1,929,261 1,731,514 Total equity $ 3,357,073 $ 3,869,243 Condensed Consolidated Statements of Operations (U.S. GAAP) (Amounts in thousands of U.S. dollars, except for shares, American Depositary Shares (ADSs), per share and per ADS data) Three Months Ended September 30, Nine Months Ended September 30, 2021 2020 2021 2020 (Unaudited) (Unaudited) Revenue: Product revenue, net $ 192,461 $ 91,080 $ 437,202 $ 208,774 Collaboration revenue 13,979 — 525,102 — Total revenues 206,440 91,080 962,304 208,774 Expenses: Cost of sales - products 47,413 21,123 116,361 49,579 Research and development [1] 351,937 349,070 1,028,754 939,340 Selling, general and administrative 269,227 160,837 683,622 391,967 Amortization of intangible assets 188 187 563 658 Total expenses 668,765 531,217 1,829,300 1,381,544 Loss from operations (462,325) (440,137) (866,996) (1,172,770) Interest (expense) income, net (2,230) (614) (11,275) 7,184 Other income, net 31,477 5,711 26,487 29,368 Loss before income taxes (433,078) (435,040) (851,784) (1,136,218) Income tax benefit (19,223) (8,423) (24,083) (8,344) Net loss (413,855) (426,617) (827,701) (1,127,874) Less: Net loss attributable to noncontrolling interest — (1,393) — (3,713) Net loss attributable to BeiGene, Ltd. $ (413,855) $ (425,224) $ (827,701) $ (1,124,161) Net loss per share attributable to BeiGene, Ltd.: Basic and diluted $ (0.34) $ (0.37) $ (0.69) $ (1.07) Weighted-average shares outstanding: Basic and diluted 1,205,971,284 1,148,973,077 1,196,391,201 1,052,940,583 Net loss per ADS attributable to BeiGene, Ltd. Basic and diluted $ (4.46) $ (4.81) $ (8.99) $ (13.88) Weighted-average ADSs outstanding: Basic and diluted 92,767,022 88,382,544 92,030,092 80,995,429 [1] Research and development expense for the three and nine months ended September 30, 2021 includes upfront fees related to in-process research and development of in-licensed assets totaling nil and $53.5 million, respectively, compared to $66.5 million and $109.5 million in the comparable prior year periods. About BeiGene BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are expediting development of our diverse pipeline of novel therapeutics through our own capabilities and collaborations. We are committed to radically improving access to medicines for two billion more people by 2030. BeiGene has a growing global team of over 7,700 colleagues across five continents. To learn more about BeiGene, please visit and follow us on Twitter at @BeiGeneGlobal. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding clinical data for BeiGene’s drug candidates and approvals of its medicines; the conduct of late-stage clinical trials and expected data readouts; additional planned product approvals and launches; the advancement of and anticipated clinical development, regulatory milestones and commercialization of BeiGene’s medicines and drug candidates; the success of BeiGene’s commercialization efforts and revenue growth; the expected capacities and completion dates for the Company’s manufacturing facilities under construction; the timeline for the Company to complete its proposed public offering and listing on the STAR Market of the Shanghai Stock Exchange, if at all; the impact of the COVID-19 pandemic on the Company’s clinical development, regulatory, commercial and other operations; BeiGene’s plans and the expected events and milestones under the caption “Recent Business Highlights and Upcoming Milestones”; and BeiGene’s plans, commitments, aspirations and goals under the captions “About BeiGene”. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; the impact of the COVID-19 pandemic on BeiGene’s clinical development, regulatory, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law. XGEVA®, BLINCYTO®, and LUMAKRAS® are registered trademarks of Amgen. ABRAXANE® is a registered trademark of Abraxis Bioscience LLC, a Bristol Myers Squibb company.