其他
总营收增长186.3%，核心产品增长近7倍！复宏汉霖要从biotech走向biopharma
复宏汉霖董事长、执行董事兼首席执行官
张文杰先生
2021年是复宏汉霖全面创新升级的一年，我们持续推动从Biotech到Biopharma的进化历程。2021年，我们全速推进研发、生产及商业运营三个板块发展，努力向更高价值链延伸，加速形成增长新动能，不断构建发展新格局。我们真诚感念各位投资人和社会各界一路以来的支持与信任，我和汉霖同仁们将继续保持‘创业、创新、创建’的企业精神，共绘中国生物制药发展蓝图！
商业化迈入新阶段，汉曲优销售创新高
汉利康®（利妥昔单抗）是中国首个生物类似药，自2019年获批上市以来已惠及超10万名中国患者。汉利康®（利妥昔单抗）由江苏复星团队负责中国的销售推广，2021年公司基于与合作伙伴约定的利润分成安排获得销售收入约人民币5.425亿元，授权许可收入约1040万元。目前汉利康已获批用于非霍奇金淋巴瘤、慢性淋巴细胞白血病及原研在中国未获批的类风湿关节炎适应症的治疗，是中国获批适应症最多的利妥昔单抗。该产品具有100mg/10ml和500mg/50ml两种规格，便于患者组合使用实现灵活用药。2022年2月，汉利康®新增类风湿关节炎适应症，以低频次给药、药效持久等优势有效改善患者生活质量，惠及更广泛患者群体。
汉达远®（阿达木单抗）于2020年12月获批准上市，是公司首款自身免疫疾病领域的单抗生物药，用于类风湿关节炎、强直性脊柱炎、银屑病和葡萄膜炎的治疗。汉达远®国内商业销售由江苏万邦负责，截至2021年底，公司基于与合作伙伴约定的利润分成安排获得销售收入约2180万元及授权许可收入100万元。复宏汉霖积极拓展汉达远®的海外布局，于2022年2月与Getz Pharma达成合作，授予其在巴基斯坦、菲律宾、肯尼亚等11个国家汉达远®的商业化等权益，助推公司商业化全球布局。
汉贝泰®（贝伐珠单抗）是复宏汉霖旗下肿瘤领域又一产品，于2021年12月获得中国国家药品监督局（NMPA）批准，用于治疗转移性结直肠癌及晚期、转移性或复发性非小细胞肺癌。复宏汉霖负责该产品在国内的销售推广，2022年将积极推进其医保准入、招标挂网和医院准入等工作，并实现医保双通道支付省市的逐步放量。此外，公司计划于2022年递交汉贝泰®新增复发性胶质母细胞瘤，肝细胞癌，上皮性卵巢癌、输卵管癌或原发性腹膜癌以及宫颈癌适应症的补充申请。
H药获批在即，PD-1国际III期临床数据亮眼
创新驱动价值增长，稳步推进全球研发布局
复宏汉霖亦通过许可项目引进的方式，加速扩充创新潜力靶点，公司引进的创新产品HLX208（BRAF V600E抑制剂）已获NMPA批准开展临床试验，有潜力与公司自有管线的多个产品产生协同效应，并在肺癌、结直肠癌等疾病领域打造更优质的差异化创新产品组合。近期，HLX208已在罕见病BRAF V600E突变型成人朗格汉斯组织细胞增生症（LCH）和Erdheim-Chester病（ECD）患者中完成首例受试者给药，后续公司将挖掘更多潜在适应症，惠及更多患者。
加速产能扩增，增强商业化保障
前行路上，在继续卓越商业化的同时，复宏汉霖将以未被满足的临床需求为创新方向，进一步夯实“内外兼修”的多元化开发策略，深耕创新研发的同时提升“研产销一体化”能力，向更具规模化和市场竞争力的Biopharma进化。
关于复宏汉霖
复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖20多种创新单克隆抗体，并全面推进基于自有抗PD-1单抗斯鲁利单抗的肿瘤免疫联合疗法。继国内首个生物类似药汉利康®（利妥昔单抗）、中国首个自主研发的中欧双批单抗药物汉曲优®（曲妥珠单抗，欧盟商品名：Zercepac®）、汉达远®（阿达木单抗）和汉贝泰®（贝伐珠单抗）相继获批上市，创新产品斯鲁利单抗MSI-H实体瘤的上市注册申请已纳入优先审评审批程序，斯鲁利单抗鳞状非小细胞肺癌适应症的上市注册申请也正在审评中。公司亦同步就12个产品、9个免疫联合治疗方案在全球范围内开展20多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。
Based on unmet clinical needs, Henlius also continues to unleash innovation potential by enhancing in-house capabilities and strengthening collaboration on external innovative assets. In 2021, the company's R&D expenditure reached approximately RMB 1.76 billion. During the Reporting Period, the company saw robust clinical progress in 12 projects and received multiple clinical approvals on 6 candidates and 1 combination therapy worldwide. As of the Latest Practicable Date, more than 70 clinical trials have been approved worldwide, and more than a total of 20 clinical trials have been carried out in various countries and regions, including China, the European Union (EU), the United States (U.S.), Australia, the Philippines, and Turkey.
Wenjie Zhang, Chairman, Executive Director and Chief Executive Officer of Henlius, remarked: “In 2021, we made significant progress on our innovation agenda as well as the evolution from a biotech company to a biopharma. We will continue to extend the breadth of our value chain and refuel our momentum for development. Our heartfelt gratitude goes to shareholders and communities for your great support and trust. Staying true to our spirit of ‘entrepreneurship, innovation and creation,’ we will do all we can for the development of China biopharmaceuticals.”
Accelerating the commercialization to step into a new stage
HANQUYOU (trastuzumab, Zercepac® in Europe) is the core anti-tumour product of Henlius indicated for the treatment of HER2 positive breast and gastric cancer patients, benefiting more than 40,000 patients to date. It is the first product commercialized by the company’s in-house commercial team that lays a favorable foundation for the overall increase in the sales of HANQUYOU. In 2021, HANQUYOU launched a new dosage form of 60mg. Together with the 150 mg form, HANQUYOU can flexibly meet the clinical medication needs of breast cancer patients with different body weights through more dosage forms and provide patients with personalized and more economical treatment plans. Moreover, Henlius is actively building an international commercial network for HANQUYOU and has joined forces with overseas partners such as Accord, a global pharmaceutical company, to promote the commercialization of Zercepac® in Europe, the Middle East and North Africa. In 2021, Zercepac® (150mg) has been successfully launched in nearly 20 European countries and regions, including the United Kingdom, Germany, France, Switzerland, and Spain. The new dosage forms of 60mg and 420mg were also approved in 2021 for marketing in the EU region. In addition, Henlius signed an agreement with Accord's parent company, Intas, to further increase commercialization licenses in U.S. and Canada and its BLA is expected to be submitted to U.S. Food and Drug Administration (FDA) in 2022. To date, HANQUYOU has access to more than 80 countries and regions, spanning both mature and emerging markets.
HANLIKANG (rituximab injection) is the first-ever China-manufactured biosimilar approved by the National Medical Products Administration (NMPA) in 2019. As of now, it has benefited more than 100,000 Chinese patients. The domestic commercial sales of HANLIKANG is being handled by Jiangsu Fosun, a subsidiary of Fosun Pharma. In 2021, HANLIKANG (rituximab) received a profit-sharing of RMB 542.5 million from Fosun Pharma and licensing revenue of RMB 10.4 million. Up to date, HANLIKANG has been approved by NMPA for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis (RA) for which the originator rituximab has not been approved in China, making it the rituximab with the most approved indications in China. This product is available with 2 dosage forms, 100mg/10ml and 500mg/50ml, allowing for more flexible drug dosing. In February 2022, HANLIKANG was approved for RA as the first rituximab approved for this indication in China. It will effectively improve patients’ quality of life with the advantages of low-frequency administration and long-lasting efficacy, reaching a broader patient population.
HANDAYUAN (adalimumab injection) is the company’s first monoclonal antibody for autoimmune diseases and was approved by the NMPA in December 2020. It is indicated for RA, ankylosing spondylitis, plaque psoriasis and uveitis. Jiangsu Wanbang is responsible for the commercial sales of HANDAYUAN in China. By the end of 2021, the company received a profit-sharing of RMB 21.8 million and licensing revenue of RMB 1.0 million. Henlius actively expands the overseas distribution of HANDAYUAN, in February 2022, it entered into a collaboration agreement with Getz Pharma to commercialize HANDAYUAN in 11 emerging markets such as Pakistan, the Philippines, Vietnam, Nigeria, Kenya, Sri Lanka, Kazakhstan and Uzbekistan, thereby speeding up the company’s faster global commercialisation layout.
HANBEITAI (bevacizumab), approved by the NMPA in December 2021, is another marked product of Henlius in the field of oncology. It is indicated for the treatment of metastatic colorectal cancer (mCRC) and unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC). Henlius is responsible for the commercial sales of HANBEITAI in China. In 2022, the company will actively promote the product's access to basic medical insurance and hospitals, and gradually increase the sales under the ‘dual-channel’ scheme. Besides, Henlius plans to file a supplemental application for additional indications, including glioblastoma, hepatocellular carcinoma, cervical cancer, and recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in 2022.
PD-1 inhibitor serplulimab is about to be approved with outstanding readouts from Phase 3 trial in small cell lung cancer
The serplulimab (innovative anti-PD-1 monoclonal antibody) is the first innovative monoclonal antibody independently developed by Henlius and also a significant milestone in the company’s evolution toward Biopharma. Two indications of serplulimab are expected to be approved by NMPA in 2022, in which the NDA of its first indication for the treatment of microsatellite instability-high (MSI-H) solid tumours has been accepted with priority review and is expected to be approved in the first half of 2022. An NDA for another indication, locally advanced and metastatic squamous non-small cell lung cancer (sqNSCLC), has also been accepted. In preparation for the launch of serplulimab, Henlius aimed to recruit around 200 people within 2022 and quickly implement a differentiated strategy for market penetration.
With serplulimab as the backbone, a total of 9 immuno-oncology combination therapies clinical trials are ongoing worldwide in a wide variety of high-incidence solid tumours, including lung cancer (LC), hepatocellular cancer, esophageal carcinoma, head and neck carcinoma, gastric cancers, etc. Henlius has carried out a comprehensive first-line treatment layout for LC in sqNSCLC, nsNSCLC and small cell lung cancer (SCLC), which covers more than 90% of lung cancer patients. Two international multi-center Phase 3 clinical trials are ongoing for sqNSCLC and SCLC in China, Turkey, Poland, Georgia and other countries and regions, enrolling more than 30% of Caucasians. In December 2021, the Phase 3 clinical study (ASTRUM-005) of serplulimab in combination with chemotherapy for the treatment of SCLC met the primary study endpoint of the overall survival (OS) with remarkable readouts and the NDA in China and the EU are expected to be submitted in 2022, making serplulimab potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. By the end of 2021, over 2,800 patients have been enrolled worldwide. The company has accumulated abundant international clinical research data that can strongly support future fillings in mainstream markets such as U.S. and the EU.
The pipeline expansion is fueled by innovation, resulting in a robust global R&D layout
Rooted in unmet medical needs, Henlius strives to promote its innovation and R&D capabilities. Synergising the Innovation centres in China and the US, the company continues the momentum for a diversified innovation with independent development accounts for over 80% of the product pipeline by enhancing internal innovation capacities and reaching out to more strategic partners. The company aggressively pushes its early R&D research capabilities further while also upgrading its technology platform. Henlius is currently looking into novel coupling techniques in effort to grow its presence in antibodies and oncology, while also focusing on the non-oncology therapeutic areas such as metabolism, cardiovascular, inflammation, etc., with the aim of advancing candidates for a promising pipeline.
In 2021, Henlius promoted in-depth research and development, unlocking the potential of the novel candidate targets including TIGIT, 4-1BB, BRAF V600E, LAG-3, CD73, etc. The two potential first-in-class bispecific antibodies, HLX301 (anti-PD-L1×TIGIT bispecific antibody) and HLX35 (anti-4-1BB×EGFR bispecific antibody), has completed the first subject dosing in Phase 1 clinical study in Australia. Meanwhile, the company’s new ophthalmic preparation product HLX04-O (anti-VEGF monoclonal antibody), independently developed through optimizing the prescription, specifications and production processes of HANBEITAI, was approved to carry out clinical trials in China, Australia, U.S., the EU, Singapore, and other countries. The company will advance the international multi-center clinical trials in 2022. In addition, a Phase 2 clinical trial of HLX22, an anti-human epidermal growth factor receptor-2 (HER2) humanized monoclonal antibody injection, in combination with HANQUYOU and chemotherapy as first-line therapy for HER2-positive locally advanced or metastatic gastric cancer patients has completed the first subject dosing in 2021.
Henlius has also committed to replenishing the innovative candidate targets through in-licensing. The company’s in-licensed product HLX208 (BRAF V600E inhibitor) has been approved by the NMPA for conducting clinical trials. It has the potential to be used in combination with the company’s multiple candidate targets and create new combinations that unlock additional indications such as LC and mCRC. Recently, it has been dosed in patients with Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) with BRAF V600E mutation. Next, Henlius will tap its potential for a broader range of indications and patients.
Integrated manufacturing platform ensures high-quality large-scale production
The company continue to build an integrated manufacturing platform, translating its R&D efforts into social impact and commercial results. The company’s commercial capacity reached 24,000L in 2021, and that in 2022 is expected to double. Towards 2025, the design capacity is planned to rise from 84,000L to 144,000L. In 2021, Xuhui facility, certificated by China and the EU GMP earlier, has ramped up its capacity from 20,000L to 24,000L. The company is also exploring localized alternatives for key materials and process development approaches to mitigate the risk of supply shortages and a lack of supporting facilities under the current international situation. Moreover, the Phase I project of Songjiang First Plant was approved for the manufacturing of HANQUYOU with the goal of putting its constructed 24,000L capacity into operation in 2022 and passing the FDA GMP inspection in the first half of 2023. The Phase I project of Songjiang Second Plant has a planned total capacity of 96,000L to get Henlius well positioned for its fast-growing industry transformation and global commercialisation blueprint. In detail, the first and second stages of this project aim to achieve a total capacity of 36,000L. They are expected to enter trial production and relevant verifications in the second half of 2022. In addition, plans are underway for the third stage of this project. The construction of its 60,000L capacity is scheduled to commence in 2022.
While ramping up capacity progress, the company is determined to accelerate the development and industrialisation of advanced production techniques such as continuous manufacturing technology and achieve economies of scale, leading to a rapid decline in the cost of its products and a streamlined manufacturing process. In 2021, the company successfully launched China’s first continuous manufacturing clinical production workshop to achieve end-to-end continuous production and thus improving productivity with stable and controllable quality.
Going forward, Henlius will keep its innovation momentum pivoting on unmet clinical needs, continue to round out its diversified development strategy of enhancing in-house capabilities and strengthening collaboration on external innovative assets, and intensify efforts to foster innovation and make great progress in R&D, manufacturing and commercialisation, evolving into a more full-fledged biopharma with keener competitiveness.
About Henlius
Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) and has continued to explore immuno-oncology combination therapies with proprietary serplulimab (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, Zercepac® in in Europe), the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the NDA of innovative product serplulimab indicated for MSI-H solid tumors has been granted priority review, and the NDA of serplulimab for the treatment of squamous non-small cell lung cancer is also under review. What's more, Henlius has conducted over 20 clinical studies for 12 products and 9 combination therapies worldwide, expanding its presence in major market as well as emerging market.
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