The board of directors of Lepu Biopharma Co., Ltd. announced that, the National Medical Products Administration (the "NMPA") has recently granted conditional marketing approval in China for PUYOUHENG (Pucotenlimab Injection), a humanized antagonist monoclonal antibody to human programmed cell death protein 1 ("PD-1"), which can antagonize the PD-1 signal to restore the capability of the immune cells to kill cancer cells through blocking PD-1 binding to their ligands PD-L1 and PD-L2, for the treatment of patients in high levels of microsatellite instability/deficient mismatch repair ("MSI-H/dMMR") solid tumors: including patients with advanced colorectal cancer who have experienced disease progression after previous therapy with fluorouracil, oxaliplatin and irinotecan as well as patients with other advanced solid tumours who have experienced disease progression after previous first-line therapy and no satisfactory treatment alternatives. Microsatellite instability ("MSI") refers to any change in microsatellite length due to either insertion or deletion of repeating units in a microsatellite in a tumor, compared to normal tissue, leading to the appearance of new microsatellite alleles. The impairment of the mismatch repair ("MMR") system can cause such changes.

Microsatellite instability-high ("MSI-H") or deficient mismatch repair ("dMMR") has been observed in various cancers, the occurrence rate of which in endometrial cancer, colorectal cancer or gastric cancer, and other cancers is nearly 30%, about 20% and about or less than 5%, respectively. MSI-H/dMMR tumors are more likely to respond to immunotherapies than tumors with fewer mutations due to the significantly increased number of somatic mutations which express a large number of neoantigens. PUYOUHENG (Pucotenlimab Injection) is a humanized immunoglobulin G4 mAb against human PD-1 independently developed by the Company, which can bind with PD-1 with high affinity to restore the capability of the immune cells to kill cancer cells by blocking PD-1 binding to their ligands PD-L1 and PD-L2.

PUYOUHENG (Pucotenlimab Injection) employs an innovative molecular design to extend its half-life and demonstrated strong clinical anti-tumor activity and a favorable safety profile. It innovatively employs antibody engineering techniques to introduce triple mutations in Fc portion to increase FcRn binding, thereby significantly improving its half-life and leading to encouraging clinical efficacy and drug compliance of patients. Compared with all competing anti-PD-1 antibodies that were marketed or had entered a Phase III clinical trial, PUYOUHENG (Pucotenlimab Injection) demonstrated an average half-life of 21.8 days (single dose).

Furthermore, the extension of the half-life did not cause any additional adverse event, and it has shown encouraging clinical efficacy profile. The approval is mainly based on a multi-center, open-label, Phase II clinical study, the primary endpoint of which is the objective response rate (the "ORR") evaluated by the Independent Review Committee (the "IRC") according to RECIST1.1. As of December 4, 2021, the study had enrolled a total of 100 patients with histologically diagnosed advanced solid tumors which were identified by the central laboratory as MSI-H/dMMR tumors. The enrolled patients received intravenous drip of PUYOUHENG (Pucotenlimab Injection) once every three weeks ("Q3W") at the dose level of 200 mg.

The median follow-up period for the population was 22.5 months, and the ORR was 49.0% (95% CI: 38.86%, 59.20%) with 9 patients realizing complete response and 40 patients realizing partial response; in the subgroup of patients with colorectal cancer who had failed treatment with triple therapy (fluorouracil, oxaliplatin and irinotecan), the ORR was 50.0% (95% CI: 31.30%, 68.70%). The results of the study indicate that PUYOUHENG (Pucotenlimab Injection) as monotherapy is safe and efficacious for the treatment of patients with advanced unresectable or metastatic MSI-H/dMMR tumors that failed prior standard treatment, the expected clinical endpoints have been achieved and the patients can gain significant benefits from the treatment.