Henlius Receives NMPA Approval for its First Innovative Monoclonal Antibody HANSIZHUANG

SHANGHAI, March 25, 2022 /PRNewswire/ -- Shanghai Henlius Biotech, Inc. (2696.HK) announced that its first self-developed innovative PD-1 inhibitor HANSIZHUANG (generic name: serplulimab injection) has been approved by the National Medical Products Administration (NMPA) for the treatment of adult patients with advanced unresectable or metastatic MSI-H (Microsatellite Instability-High) solid tumors that have failed to respond to previous standard treatments, providing an alternative treatment option for patients. Furthermore, it also empowers the domestic precision immunotherapy for tumors and promotes the high-quality development of China's biopharmaceutical industry.

Zhang Wenjie, Chairman, Executive Director, and CEO of Henlius, said, "I'm very glad to see the first indication of HANSIZHUANG was approved in China. As one of the pioneering PD-1 inhibitors for the 'pan-cancer' treatment of MSI-H solid tumors in China, HANSIZHUANG would give full play to its advantages in clinical practice to enable patients to live longer with more comfortable lives and accelerate the development of tumor immunotherapy. In addition, HANSIZHUANG is the fifth product launched by Henlius as well as a significant milestone in the company's evolution toward Biopharma, which will actively drive Henlius to move forward, and inspire more innovative achievements centered on patient needs."

Professor Qin Shukui, one of the co-leading principal investigators of the pivotal phase II clinical study of HANSIZHUANG on MSI-H solid tumors, from the Tumor Center of Nanjing Jinling Hospital, said, "PD-1 inhibitor is one of the immune checkpoint inhibitors that has been explored in some diseases, which makes breakthroughs in many tumor treatments. The clinical research data of HANSIZHUANG for MSI-H solid tumors is outstanding and will actively improve the clinical efficacy and provide a new mindset and alternative option for the precision treatment for tumors in China."

Professor Li Jin, another co-leading principal investigator of the pivotal phase II clinical study of HANSIZHUANG on MSI-H solid tumors, from the Department of Oncology, Shanghai East Hospital, Tongji University, mentioned, "the approval of HANSIZHUANG brings new hope to patients with MSI-H solid tumors and better meets the demand of clinical treatment and medication of tumors. While promoting the development of domestic tumor treatment, this product plays a positive role in enhancing the recognition of 'pan-cancer' treatment and promoting the development of tumor precision immunotherapy."

"Pan-cancer" treatment benefits a broader patient population

The approval is mainly based on a single-arm, multi-center, pivotal phase II clinical study. The primary efficacy endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST v1.1. As of July 10, 2021, 108 patients were enrolled, in which 68 patients with MSI-H confirmed by central laboratory or study sites were included in the main efficacy analysis population (MEAP). IRRC assessed ORR were 39.7% (95% CI: 28.03, 52.30; 3 CR, 24 PR) in MEAP. The study concludes that HANSIZHUANG monotherapy could bring significant benefits in the treatment of unresectable or metastatic MSI-H solid tumors that have failed to respond to previous standard treatments, met the primary endpoint criteria, and had good safety and tolerability. The results of this clinical study were first presented in oral at the 24^th annual meeting of Chinese Society of Clinical Oncology (CSCO).

"Microsatellite" is a class of short tandem repeat DNA sequence in genes. It is called microsatellite instability (MSI) due to the change of microsatellite sequence length caused by insertion or deletion during DNA replication ^[1]. Many studies have shown that MSI is closely related to tumorigenesis, so in clinical practice, MSI is an important biomarker reference for the prognosis of some solid tumors and adjuvant treatment plans. MSI-H is one of the MSI types, in which two or more spots change, and commonly found in endometrial cancer, colorectal cancer, and gastric cancer, etc. These patients usually have high response to immune checkpoint inhibitors ^[2-3] . PD-1/PD-L1, important immunosuppressive molecules, have good therapeutic effect for patients with MSI-H solid tumors. It is estimated that there are more than 300,000 new MSI-H tumor patients in China every year ^[4] , and some of them have no access to effective treatment. Furthermore, there are few PD-1 inhibitors approved for MSI-H advanced solid tumors in China currently. The clinical treatment demand is far from being met. Therefore, the advent of HANSIZHUANG is a "weapon" for the treatment of MSI-H solid tumors in China. It is expected to enhance the clinical diagnosis and tumor treatment with unique innovation and superior quality in clinical practice to achieve maximum benefit for patients and promote the construction of tumor prevention and treatment system.

Leverage the world-class quality to explore overseas market

With HANSIZHUANG as the backbone, Henlius conducts and accelerates various clinical trials with immuno-oncology combination therapies worldwide in a wide variety of high-incidence solid tumors, including lung cancer (LC), esophageal carcinoma, head and neck carcinoma, gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. Up to date, more than 2,800 subjects have been enrolled worldwide for HANSIZHUANG clinical trials, which makes it a PD-1 inhibitor with one of the largest global clinical data pools and lays a solid foundation for future applications across the world. On the other hand, two global multi-center phase III clinical trials regarding sqNSCLC and ES-SCLC are conducted in China, Turkey, Poland, Georgia and other countries and regions, in which the Caucasian accounts for more than 30% of the total enrolled subjects, providing more diverse cases for clinical research. The NDA of the treatment for locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC) has been accepted by the NMPA and is expected to be approved in 2022. The global multi-center phase III study of HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC met the primary study endpoint of the overall survival (OS) with remarkable readouts. Its NDA in China and MAA in the EU are expected to be filed in 2022, making HANSIZHUANG potentially the world's first PD-1 inhibitor for the first-line treatment of SCLC.

Henlius actively explores overseas commercialization of HANSIZHUANG, while proceeding its global multi-center clinical research. As early as 2019, the company forged a partnership with PT Kalbe Genexine Biologics（KG Bio）to grant it an exclusive license to develop and commercialize HANSIZHUANG in relation to a monotherapy and two combination therapies in 10 Southeast Asian countries. Going forward, Henlius will continue to expand global commercialization layout of HANSIZHUANG to reach out to more countries and regions, which urges this product to step on to the world PD-1 stage and benefits a broader patient population worldwide with its world-class quality.

In the future, Henlius will keep focusing on patient needs and inspire more "made-by-Henlius" products with efficient and innovative in-house capabilities, aiming to provide highest quality solutions and services for patients in China and across the world and to build a national brand in biopharmaceutical industry.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. It is approved by the NMPA for the treatment of MSI-H solid tumors. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies of HANSIZHUANG worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. Up to date, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDA of the treatment for squamous non-small cell lung cancer (sqNSCLC) has been accepted by the NMPA and is expected to be approved in 2022. Furthermore, the global multi-center phase 3 clinical study of HANSIZHUANG in combination with chemotherapy in previously untreated extensive small-cell lung cancer (ES-SCLC) met the primary endpoint of overall survival (OS) with remarkable readouts and its NDA in China and MAA in the EU are expected to be filed in 2022, making this product potentially the world's first anti-PD-1 mAb for the first-line treatment of SCLC.