The board of directors of the Shanghai Junshi Biosciences Co., Ltd. announced that the Company has received the Acceptance Notice issued by the National Medical Products Administration and the supplemental new drug application (?NDA?) for the Company's product toripalimab (trade name: TUOYI ®, product code: JS001), in combination with bevacizumab for the first-line treatment of unresectable or metastatic hepatocellular carcinoma (?HCC?) patients has been accepted. Drug name: Toripalimab Injection; Application matter: Registration of Domestic Production of Pharmaceutical Product; Acceptance Nos.: CXSS2400069, CXSS2400070; Applicant: Shanghai Junshi Biosciences Co., Ltd.; Review conclusion: It is decided to be accepted upon review according to the requirements of Article 32 of the Administrative License Law of the People's Republic of China. Liver cancer is a common malignant tumor of the digestive system worldwide, and the main pathological type is HCC (accounting for about 90%).

According to data released by the GLOBOCAN for 2022, the annual number of new cases and deaths of liver cancer worldwide in 2022 was 866,000 and 759,000, respectively. China has high liver cancer incidence. In 2022, the number of new cases of liver cancer reached 368,000 (accounting for 42.4% of global cases), ranking fourth among domestic malignant tumors, with 317,000 deaths (accounting for 41.7% of global cases), ranking second among domestic malignant tumors.

Due to the insidious onset, about 70%-80% of liver cancer patients in China are already at intermediate or advanced stage at first diagnosis, with a median OS of only approximately 10 months and a five-year survival rate of approximately 12%. In recent years, with the continuous emergence of the combination therapy based on the immunotherapeutic drugs, the treatment pattern of advanced liver cancer has changed, and it is gradually becoming possible to achieve radical cure after down-stage transformation. The supplemental NDA is based on the HEPATORCH study (NCT04723004), which is a multi- center, randomized, open-label, active controlled phase III clinical study, aiming to evaluate the efficacy and safety of toripalimab in combination with bevacizumab for the first-line treatment of unresectable or metastatic HCC compared to the standard treatment of sorafenib.

The study was launched in 57 centers nationwide in China, led by Professor Fan Jia (, an academician of the Chinese Academy of Sciences, from Zhongshan Hospital affiliated to Fudan University as the principal investigator. In June 2024, the primary endpoints of progression free survival (?PFS?, based on independent radiological review) and overall survival (?OS?) of the HEPATORCH study met the pre-defined efficacy boundary. The results of the study showed that toripalimab in combination with bevacizumab for the first-line treatment of patients with advanced HCC could significantly prolong the PFS and OS of the patients compared with sorafenib, while improving the secondary endpoints such as objective response rate and time to progression.

The safety profile of toripalimab was consistent with the known risks, and no new safety signals were identified. The detailed data of this study would be presented at a subsequent international academic conference. Toripalimab injection is the first domestic PD-1 monoclonal antibody approved for marketing in China, and has won the ?Chinese Patent Gold Award ?, the top award in China's patent field.

Over forty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally, including in China, the United States, Southeast Asia, and Europe. Ongoing or completed pivotal clinical studies evaluating the safety and efficacy of toripalimab cover a broad range of tumor types. As of the date of this announcement, there are ten approved indications for toripalimab in Chinese mainland.

In December 2020, toripalimab injection was successfully negotiated into the National Reimbursement Drug List (the ?NRDL?) for the first time. At present, six approved indications have been included in the NRDL (2023 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for the treatment of melanoma.

In April 2024, the Drug Office, Department of Health, the Government of the Hong Kong Special Administration Region (DO) accepted the NDA for toripalimab in combination with cisplatin and gemcitabine, for the first-line treatment of adults with metastatic or recurrent locally advanced nasopharyngeal carcinoma (?NPC?), and for toripalimab, as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy. In terms of international layout, toripalimab had been approved for marketing as the first nasopharyngeal cancer drug in the United States in October 2023. In addition, the European Medicines Agency (EMA) and the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) accepted the marketing authorization application (MAA) for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic NPC, and toripalimab in combination with paclitaxel and cisplatin for the first- line treatment of patients with unresectable locally advanced/recurrent or metastatic esophageal squamous cell carcinoma.

The Australia Therapeutic Goods Administration (TGA) and the Singapore Health Sciences Authority (HSA) accepted the new chemical entity application and the NDA for toripalimab in combination with cisplatin and gemcitabine, for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and for toripalimab, as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy, respectively.