The board of directors of Alphamab Oncology announced that the updated clinical data from a phase II clinical study (study number: KN046-IST-04) of KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) combined with chemotherapy in the first-line treatment of PDAC will be presented at the 2021 annual meeting of Chinese Society of Clinical Oncology ("2021 CSCO annual meeting), a professional academic group that is voluntarily constituted by clinical oncology professionals, relevant enterprises and public institutions. The 2021 CSCO annual meeting will be held from September 25, 2021 to September 29, 2021. This is a phase II clinical trial conducted in China designed to evaluate the efficacy and safety of KN046 in combination with nab-paclitaxel/gemcitabine in the first-line treatment of locally advanced unresectable or metastatic PDAC. The enrolled patients with ECOG PS 0 to 1 received KN046 at 5mg/kg Q2W combined with nab-paclitaxel at 125mg/m2 on day 1, 8 and 15 Q4W and gemcitabine at 1000mg/m2 on day 1, 8 and 15 Q4W for 4 to 6 cycles. Patients without disease progression received single-drug maintenance therapy of KN046 at 5mg/kg Q2W. Tumor evaluation was performed in accordance with RECIST v1.1 every 8 weeks. The primary endpoint was ORR and the secondary endpoints were DCR, DOR, TTP, PFS, OS and safety. As of May 26, 2021, 29 patients were enrolled, among whom 20 (69.0%) patients were still under treatment and 17 (58.6%) patients had distant metastases. The median exposure duration of KN046 was 14.1 (2.0, 52.7) weeks. Efficacy . Among the 22 patients who underwent at least one tumor assessment, the complete response rate was 4.5% (1/22), the PR rate was 45.5% (10/22), and the stable disease rate was 45.5% (10/22). The ORR was 50.0% (95% CI: 28.2% to 71.8%) and the DCR was 95.5% (95% CI: 77.2% to 99.9%). 4 patients achieved PR after 4 to 6 cycles of treatment and received the surgical treatment, who met the criteria for surgical resection according to MDT assessment. The six-month PFS rate was 62.3% (95% CI: 30.4% to 82.9%). Safety . 29 patients were included in the safety analysis data set and the incidence rate of TRAEs was 55.2%, 27.6% of which at grade 3 or higher levels. 3 patients (10.3%) had experienced immune-related adverse events related to KN046 at grade 3 or higher levels, of whom 1 patient with skin rash and infusion reaction, 1 patient with autoimmune hepatitis, and 1 patient with elevated transaminase who was later confirmed to have biliary obstruction. The incidence rate of serious adverse events related to KN046 and adverse events related to KN046 leading to treatment termination was 3.4% and 6.9%, respectively. There were no adverse events leading to death. Conclusion: KN046 combined with nab-paclitaxel/gemcitabine in the first-line treatment of locally advanced unresectable or metastatic PDAC demonstrated excellent efficacy results and the ORR was significantly improved as compared with the traditional chemotherapy. The patients were well tolerated by the combination therapy which is expected to provide a better option to patients with advanced pancreatic cancer. KN046 is a global innovative PD-L1/CTLA-4 bispecific antibody independently developed by the Group, targeting both PD-L1 and CTLA-4 with a clear structural differentiation to improve localization with the tumor microenvironment and to reduce off-target toxicity. Currently, there are approximately 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, triple-negative breast cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, PDAC and thymic carcinoma in China, the United States and Australia. The results of these clinical trials have preliminarily shown a favorable safety profile and significant efficacy of KN046 in treatment. Among them, the preliminary results of the phase II clinical trials in China indicate promising activity of KN046 for NSCLC, PDAC and triple-negative breast cancer as a single therapy and in combination therapy with chemotherapy. The Group has published preliminary promising safety and efficacy data of KN046 in patients who have failed prior treatments with immune checkpoint inhibitors. The Group has initiated 2 pivotal phase III clinical trials in NSCLC, and a pivotal trial of KN046 in thymic carcinoma. The Group is also exploring cooperation opportunities to conduct clinical trials of KN046 in combination with its business partners' drug candidates, to achieve better therapeutic effects. The Group has adopted a fast/first-to-market approach on selecting indications and plans to submit the first biologic license application for KN046 in China in the first half of 2022. The preclinical and clinical trial results of KN046 have shown promising efficacy and indicated that KN046 is able to significantly reduce toxicity to human peripheral system. The Company believes that KN046 has the potential to become a breakthrough in cancer immunotherapy.