Shanghai, China, June 15th, 2023 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient has been dosed in a phase 2 clinical trial (NCT05584137) of HANSIZHUANG (serplulimab injection), an innovative anti-PD-1 monoclonal antibody (mAb) independently developed by the company, in combination with HLX26, an innovative anti-LAG-3 mAb for the treatment of metastatic colorectal cancer (mCRC) patients who have received third-line treatment in Chinese mainland. In addition, a phase 2 clinical trial of HANSIZHUANG in combination with HLX26 for the first-line treatment of advanced non-small cell lung cancer (NSCLC) has been approved by the National Medical Products Administration (NMPA)，recently.

Colorectal cancer is the second most common malignancy in China. There are 555,477 newly diagnosed colorectal cancer cases in 2020 in China[1] and the incidence increases with age. Metastasis happens frequently in colorectal cancers and the majority of patients with colorectal cancer are diagnosed at advanced stages[2]. The most common sites for metastasis are liver, lung and abdominal cavity, among which liver metastasis is most frequently seen. There are about 50% of all mCRC patients suffer from liver metastasis[3]. mCRC is mainly treated by surgery, radiotherapy, chemotherapy, targeted therapy or a combination of the above. With the development of immune-oncology, immune checkpoint inhibitors have shown good efficacy in a variety of solid tumours. As another promising immune checkpoint inhibitor after CTLA-4 and PD-1/PD-L1, anti-LAG-3 mAb has been shown to synergistically activate T-cell activity in combination with anti-PD-1 mAb in preclinical studies[4].

HLX26 is a human mAb targeting lymphocyte-activation gene 3 (LAG-3) extracellular domains, which was developed independently by Henlius. HLX26 can block the LAG-3-mediated signalling pathway to restore the killing function of T-cell. Pre-clinical studies proved that HLX26 has the anti-tumour effect and favourable tolerability and safety. Furthermore, in vitro and animal studies showed that HLX26 in combination with serplulimab have a significant synergistic effect in anti-tumour. These results lay the foundation for further clinical studies on combination usage. In August 2022, the first subject has been dosed for a phase 1 clinical trial of HANSIZHUANG in combination with HLX26 for the treatment of advanced/metastatic solid tumours or lymphomas.

Underpinned by the patient-centric strategy, Henlius has achieved an overall layout of the immune checkpoint products of PD-1/L1, CTLA-4, LAG-3, etc., proactively exploring immuno-oncology combination therapy. Meanwhile, Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company such as tumour-specific target, angiogenesis target, immunotherapeutic target, etc. and chemotherapy drugs to conduct immune combination therapies in a wide variety of indications, committing to bringing affordable and high-quality innovative biologics to patients around the world.

About NCT05584137

This two-stage, phase 2 clinical study aims to evaluate the efficacy, safety, and tolerability of HLX26 in combination with HANSIZHUANG in mCRC patients who have received third-line treatment. Stage 1 is a dose-escalation study following “3+3” design. Eligible subjects will be given different doses of HLX26 (500, 800, and 1600 mg) and fixed-dose HANSIZHUANG (300 mg) intravenously every 3 weeks. The primary endpoints are the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints include pharmacokinetic parameters, immunogenicity, safety, and preliminary efficacy. Stage 2 is a dose-expansion study. The primary endpoint of this stage is the objective response rate (ORR) assessed by investigator per RECIST v1.1. The secondary endpoints include other efficacy endpoints, such as progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), and overall survival (OS), as well as safety, immunogenicity, and pharmacokinetic characteristics.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 3 indications are approved for marketing in China, 2 marketing applications are under review in China and the EU, and more than 10 clinical trials are ongoing across the world.

HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC). The marketing applications of the first-line treatment for esophageal squamous cell carcinoma (ESCC) and ES-SCLC are under review by the NMPA and the EMA, respectively. Focus on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 14 clinical trials on immuno-oncology combination therapies in a wide variety of indications. As of now, the company has enrolled more than 3,500 subjects in China, the U.S., Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The results of 3 pivotal trials of HANSIZHUANG were published in theJournal of the American Medical Association (JAMA, IF: 157.3), Nature Medicine (IF: 87.241), and the British Journal of Cancer (IF: 9.075), respectively. On the other hand, HANSIZHUANG was recommended by the  CSCO Guidelines for Small Cell Lung Cancer, the  CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Guidelines for Colorectal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumors. Furthermore, Serplulimab was granted orphan drug designations by the FDA and the EC for the treatment of SCLC, and the first patient has been dosed in a bridging head-to-head trial in the United States to comparing HANSIZHUANG to standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC.

About Henlius

Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable, and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases, and ophthalmic diseases. Up to date, 5 products have been launched in China, 1 has been approved for marketing in overseas markets, 18 indications are approved worldwide, and 3 marketing applications have been accepted for review in China, the U.S., and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China GMP.

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 HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab for injection, trade name in Europe: Zercepac^®; trade names in Australia: Tuzucip^® and Trastucip^®, the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Its NDA for the treatment of esophageal squamous cell carcinoma (ESCC) is under review. What's more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets.

【References】

[1] Rui-Mei, Feng, Yi-Nan, et al. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?[J]. Cancer communications, 2019.

[2]中国结直肠癌诊疗规范（2020版）

[3] Robert P. Jonesa,b Norihiro Kokudoc Gunnar Folprechtd,et al. Colorectal Liver Metastases: A Critical Review of State of the Art [J]. Liver Cancer, 2017;6:66–71.

[4] Woo, SR et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 72, 917-927.