On December 17, 2021, Henlius held its Global R&D Day in Shanghai. Themed “Hong•Evolution H-evolution: From Biotech to Biopharma,” the event highlighted the latest achievements and progress across the company’s full product pipeline, fostering collaborative strategies for high-quality future development and steadily advancing toward becoming a biopharmaceutical company.

In his welcome address, Mr. Zhang Wenjie, Chairman, Executive Director, and CEO of Henlius, stated: “The Chinese biopharmaceutical industry is developing rapidly, and Henlius has been not only a witness but also an active participant. Since our inception, we have been committed to providing affordable, high-quality biologics to patients worldwide, continuously innovating and strategically positioning ourselves in R&D, manufacturing, and commercialization. Currently, four of our products are marketed in China, one is approved in the European Union, and three New Drug Applications (NDAs) have been accepted. Next year, we will launch our PD-1 inhibitor, serplulimab, as a flagship product, while continuing to actively explore innovative targets. Leveraging our integrated in-house R&D platform, Henlius has established a rich and comprehensive product pipeline. Nevertheless, we remain steadfast in enhancing our integrated ‘R&D, manufacturing, and commercialization’ capabilities. In the future, we will continue to prioritize independent R&D, accelerate development and expand our advantages in monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADCs), and small molecules through collaborative innovation between our Shanghai and California R&D centers. We will also rapidly scale up production capacity, further advance manufacturing technologies and supply chain capabilities to meet strong market demand. Furthermore, we will optimize our commercial footprint and build a robust commercial organization, integrating a strong global commercial network with top-tier talent. Upholding our corporate spirit of ‘entrepreneurship, innovation, and creation,’ we will progressively evolve into a larger, more competitive Biopharma company, achieving more mature and steady growth, laying a strategic foundation for future development, and better fulfilling our original aspiration and mission.”

Henlius adheres to an innovation-driven R&D strategy that strengthens both internal capabilities and external collaborations. By building efficient in-house innovation organizational capabilities, its two R&D centers work closely together and provide mutual support, enabling seamless coordination across early drug development, late-stage research, and methodology. This collaborative approach enhances R&D efficiency and accelerates innovation. At the meeting, Dr. Jean-Michel Gries, President of Henlius US, and Dr. Wenfeng Xu, Senior Vice President of Henlius US, presented Henlius’s early-stage R&D layout and its pipeline of innovative products developed for the field of tumor immunology.

Dr. Gries stated that Henlius adheres to the R&D guiding principle of “patient-centricity and technology-driven innovation.” By focusing on translational medicine and clinical development, implementing efficient project and pipeline management, and building a global talent team, the company has established a rich and diversified product portfolio covering key therapeutic areas such as lung cancer, breast cancer, and gastric cancer. Building on its commercialized biosimilar portfolio, Henlius is continuously expanding its pipeline of innovative monoclonal antibodies and bispecific antibodies, while also exploring multispecific antibodies and combination therapies to extend into disease areas beyond oncology.Dr. Xu Wenfeng added, “The essence of innovation lies in addressing unmet clinical needs. Grounded in science and guided by mechanisms of action, Henlius has leveraged the synergy between its R&D centers in China and the United States to establish an advanced and comprehensive platform encompassing antibody discovery, biological optimization, translational research, and engineered therapies. On this foundation, we focus on diverse targets to incubate a growing number of innovative product programs, including highly innovative lead molecules with strong potential competitiveness such as HLX26 (anti-LAG-3 antibody), HLX53 (anti-TIGIT antibody), HLX301 (anti-PD-L1/TIGIT bispecific antibody), and HLX35 (anti-EGFR/4-1BB bispecific antibody). Currently, there are no marketed products targeting these indications globally. The company has completed preclinical studies for these projects, with results demonstrating favorable efficacy and safety profiles, paving the way for further advancement into clinical trials.”

Clinical development plays a pivotal role in the translation of new drug discoveries into clinical applications. Mr. Zhu Jun, President of Henlius, introduced the company’s product pipeline and R&D progress across multiple disease areas, and shared insights on the company’s lean clinical operations.

For lung cancer, which has the second highest incidence rate globally, Henlius has achieved comprehensive first-line clinical coverage in this therapeutic area. Clinical trials of serplulimab have been conducted across subtypes including squamous non-small cell lung cancer (sqNSCLC), non-squamous non-small cell lung cancer (nsNSCLC), and small cell lung cancer (SCLC), covering more than 90% of lung cancer patients. Notably, the National Medical Products Administration (NMPA) has accepted the marketing authorization application for serplulimab as a first-line treatment for locally advanced or metastatic sqNSCLC. In the field of gastrointestinal tumors, the company has deeply cultivated the anti-HER2 therapeutic area, where trastuzumab biosimilar Hanquyou® in combination with chemotherapy has become the standard first-line treatment regimen for HER2-positive metastatic gastric cancer. The New Drug Application (NDA) for serplulimab, an innovative product independently developed by the company, for the indication of MSI-H solid tumors was officially included in the priority review and approval process in 2021. It is expected to be approved for marketing in the first half of 2022, becoming the first anti-PD-1 monoclonal antibody in China for the “pan-cancer” treatment of MSI-H solid tumors.

Meanwhile, Henlius is also tackling breast cancer and other solid tumors with its rich and comprehensive pipeline. The company is rapidly advancing the development of HLX208, an innovative small-molecule BRAF V600E inhibitor, while strategically positioning itself across various disease areas. By creating synergies with other investigational monoclonal antibody products targeting EGFR and PD-1 in its pipeline, Henlius aims to build a superior portfolio of differentiated innovative therapies across multiple cancer indications, thereby providing precise and comprehensive treatment options for patients with BRAF V600E mutations.

Clinical lean operations management and business development serve as the “engine” and driving force behind the agile, rapid, and high-quality product development at Henlius. The Company employs flexible clinical development strategies that are also scientifically sound to accelerate product market entry, including establishing communication channels with more than 40 regulatory authorities across 32 countries worldwide and maintaining patient enrollment rates that lead the industry, thereby supporting project operations.

The meeting also released detailed interim analysis data from the ASTRUM-005 study, a randomized, double-blind, international, multicenter, Phase III clinical trial evaluating the efficacy and safety of serplulimab (an innovative anti-PD-1 monoclonal antibody) combined with chemotherapy versus placebo combined with chemotherapy in patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC).

The study results demonstrated that serplulimab in combination with carboplatin-etoposide prolonged median overall survival (OS) in both the overall population and the Chinese subgroup. The median OS in the overall population was 15.38 months in the serplulimab group versus 11.10 months in the placebo group, representing a 38% reduction in the risk of death (41% in the Chinese subgroup; p < 0.001). The 2-year overall survival rates (OSR) for the two treatment groups were 43.2% and 8.0%, respectively, with a favorable safety profile.

In recent years, multiple PD-1 inhibitors have failed in the field of small cell lung cancer (SCLC). Previously, clinical trials of Keytruda and Opdivo as first-line treatments for SCLC did not succeed, leading to the voluntary withdrawal of their marketing applications for this indication. This outcome suggests that serplulimab is poised to become the first anti-PD-1 monoclonal antibody approved for first-line treatment of SCLC worldwide, offering a novel therapeutic option for patients with small cell lung cancer.

The international, multicenter clinical study ASTRUM-005 was led by Principal Investigator Professor Cheng Ying, Director of the Jilin Provincial Cancer Center, Director of the Jilin Provincial Lung Cancer Diagnosis and Treatment Center, and Director of the Integrated Diagnosis and Treatment Center for Malignant Tumor Clinical Research at the Jilin Provincial Cancer Hospital. The trial was conducted in multiple countries, including China, Poland (European Union), Russia, Turkey, Ukraine, and Georgia. Enrolled subjects were randomized in a 2:1 ratio into two groups to receive intravenous infusions of either serplulimab or placebo in combination with chemotherapy every three weeks, until disease progression, death, intolerable toxicity, withdrawal of informed consent, or occurrence of other reasons specified in the protocol, whichever occurred first. The primary objective of this study was to compare the clinical efficacy of the two treatment regimens as first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The secondary objectives were to evaluate the safety and tolerability of the two regimens. The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), PFS2, objective response rate (ORR), duration of response (DOR), safety, pharmacokinetic profiles, and immunogenicity.

As of October 22, 2021, a total of 585 eligible subjects were enrolled in the study (serplulimab group: n=389; placebo group: n=196), with a median follow-up time of 12.3 months. The median overall survival (OS) was 15.38 months in the serplulimab group and 11.10 months in the placebo group, with a hazard ratio (HR) of 0.62 (95% CI: 0.48, 0.80; p < 0.001). The 2-year OS rates were 43.2% and 8.0% in the two treatment groups, respectively. In the Asian population, the median OS was 16.03 months in the serplulimab group and 11.10 months in the placebo group, with an HR of 0.59 (95% CI: 0.44, 0.79; p < 0.001). The trial results demonstrated that serplulimab combined with carboplatin-etoposide significantly improved OS in patients with first-line extensive-stage small cell lung cancer (ES-SCLC) and exhibited a favorable safety profile. On December 7, based on the prespecified interim analysis conducted by the Independent Data Monitoring Committee (IDMC), the IDMC recommended early submission for approval based on these efficacy results.

Henlius President Zhu Jun stated, “For the ASTRUM-005 study in small cell lung cancer, we engaged in multiple rounds of communication with regulatory authorities during the initial protocol design phase regarding the primary and secondary endpoints, patient representativeness, and the overall study plan, ultimately finalizing the current large-sample study design. The trial enrolled 585 patients across 128 centers, with 30% of participants from outside China.”

Currently, there are no positive trial results based on this study available globally. Henlius has stated that it will submit the marketing authorization application for this indication as soon as possible. In the future, the company will continue to prioritize patient needs and actively advance the international clinical registration of serplulimab-based combination immunotherapies and products, bringing benefit to more patients worldwide.

2021 was a pivotal year for Henlius to further expand the advantages of its comprehensive, integrated manufacturing platform. Ms. Huang Wei, Chief Operating Officer and Senior Vice President of Henlius, shared insights on topics such as capacity planning, quality system development, and advanced manufacturing processes. The company has continuously advanced capacity construction across its three major bases. The Xuhui base currently has a capacity of 24,000 liters, with GMP production batches exceeding 300 by the end of 2021. To support future capacity expansion, Phase I of the Songjiang Base (I) has completed construction of its 24,000-liter capacity, while Phase I of the Songjiang Base (II) is designed for a capacity of 36,000 liters. The company’s total production capacity is expected to reach 48,000 liters in 2022 and 84,000 liters within three years. Meanwhile, its quality system, benchmarked against international standards, provides competitive advantages for Henlius’s global manufacturing capabilities. Henlius’s quality management system has successfully undergone multiple on-site inspections and audits conducted by the China National Medical Products Administration (NMPA), the European Medicines Agency (EMA), EU Qualified Persons (QPs), and the company’s international commercial partners. Notably, the Xuhui production site has obtained GMP certification from both China and the European Union. Furthermore, Henlius continues to upgrade and optimize its processes, exploring the application of advanced manufacturing technologies. It has established China’s first GMP-compliant continuous clinical production facility, successfully achieving end-to-end continuous manufacturing, which effectively enhances production capacity while ensuring stable and controllable product quality.

While continuously expanding production capacity, the Company is also actively building a comprehensive and innovative business operation model. Mr. Yu Cheng, Chief Commercial Officer and Vice President of Henlius, stated that establishing a patient-centric ecosystem and enhancing marketing efficiency are the focal points of Henlius’s commercial strategy. Taking Hanquyou® (trastuzumab) as an example, thanks to its superior cost-effectiveness in commercialization compared to industry peers, the product has entered a period of rapid growth. We will continue to empower long-term, sustainable business growth through multi-dimensional collaborations with partners in areas such as drug market access, and by steadily building the “Leave No HER2-Positive Patient Behind” ecosystem. Furthermore, the Company plans to launch a new product next year: the PD-1 inhibitor serplulimab. As a rising star in immunotherapy, serplulimab is poised to become the first PD-1 inhibitor approved for the indication of MSI-H solid tumors, while also providing new treatment options for patients with small cell lung cancer (SCLC) worldwide. With significant commercial potential, its future prospects are highly promising.

As a responsible, international, innovative biopharmaceutical company, Henlius is patient-centric, focusing on unmet clinical needs and creating more possibilities through innovation. During the conference’s roundtable forum, experts discussed treatment approaches and future developments for lung cancer, colorectal cancer, and solid tumors. Professor Han Baohui from Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, stated, “Immunotherapy has become the mainstay for treating lung tumors, particularly in patients with high PD-L1 expression, where PD-1 inhibitors can enable chemotherapy-free regimens while achieving satisfactory efficacy. Moving forward, we need to continue exploring effective combinations of PD-1 inhibitors with other therapeutic modalities. By prioritizing safety and efficacy, we can encourage the development of more efficient combination therapy models, thereby benefiting more patients.” Professor Cai Sanjun from Fudan University Shanghai Cancer Center noted, “Unlike lung cancer, the treatment of colorectal cancer remains primarily surgical. However, in advanced-stage disease, the efficacy of targeted and immunobiologic agents such as cetuximab and bevacizumab is well recognized. Henlius’s PD-1 inhibitor, serplulimab, has demonstrated promising efficacy in small cell lung cancer and holds potential for broader application in colorectal cancer treatment. We look forward to breakthroughs with serplulimab-based combination regimens, leveraging their strong synergistic effects, particularly in the treatment of advanced colorectal cancer.” Professor Peng Junjie from Fudan University Shanghai Cancer Center added, “Over the next five years, chemotherapy is expected to remain the cornerstone of colorectal cancer treatment, with the addition of targeted and immunotherapies yielding improved outcomes. In precision medicine, we recommend guiding drug development with biomarkers to advance the diagnosis and treatment of colorectal cancer.”

Henlius has proactively established a diversified and leading product pipeline focused on oncology, autoimmune diseases, and other therapeutic areas. Guided by unmet clinical needs as the direction for innovation, Henlius is committed to benefiting more patients. Looking ahead, Henlius will remain steadfast in its commitment to independent innovation and high-quality supply, continuously expand and optimize its product pipeline, and accelerate the enhancement of its product value chain. By bringing health and hope to more patients, advancing toward becoming a biopharmaceutical company (Biopharma), and forging a new paradigm for development, Henlius aims to shape a new landscape for sustainable growth.