Akeso, Inc. (09926.HK) announces that Cadonilimab (PD-1/CTLA-4 bi-specific antibody), the  first-inclass novel immuno-oncology drug independently developed by the Company, combined with Ivonescimab (PD-1/VEGF bi-specific antibody), the novel immuno-oncology drug independently developed by the Company, has obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the People's Republic of China to initiate a phase Ib/II clinical trial with or without chemotherapy for the treatment of advanced non-small cell lung cancer (NSCLC).

This clinical trial is the world's first 'bi-specific antibody' plus 'bi-specific antibody'combination therapy that has entered the clinical trial stage. The combined application of two novel PD-1 based bi-specific antibody drugs is expected to further enhance the clinical effect of immunotherapy on the basis of the existing immunotherapy based on PD-1/PD-L1 inhibitors. This clinical trial is also another important manifestation of the Company's full exploration of the clinical value and commercial value of its abundant drugs under research.

Ivonescimab has shown good safety and tolerability in early clinical trials on various types of lung cancer including NSCLC and SCLC. It has also shown excellent anti-tumor effects: the ORR of Ivonescimab combined with chemotherapy in the treatment of PD-L1 positive non-squamous NSCLC was 83.3% (N=6), and the ORR of PD-L1 negative non-squamous NSCLC was 45.5% (N=11); the ORR of Ivonescimab combined with chemotherapy in NSCLC treatment where epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment failed reached 60.0% (N=5); the ORR of Ivonescimab combined with chemotherapy in the treatment of PD-L1 relapsed or refractory NSCLC was 50.0% (N=4); and the ORR of Ivonescimab combined with chemotherapy in the first-line treatment of SCLC was as high as 100.0% (N=5).

The ongoing phase Ib/II clinical trial of Cadonilimab combined with Anlotinib (an antiangiogenic tyrosine kinase inhibitor (TKI) drug) for the treatment of advanced NSCLC also suggests that there is a good synergistic effect between Cadonilimab and anti-angiogenesis therapy, which can further improve anti-tumor activity.

In addition, the results of multiple clinical trials in the industry have fully shown the clinical value of the combination therapy of PD-1 and CTLA-4 targets in NSCLC. Since antiangiogenesis therapy can normalize tumor blood vessels and make tumor microenvironment more suitable for immunotherapy, immuno-inhibitors combined with anti-angiogenic drugs have become one of the most popular drug combinations in tumor therapy. The field of lung cancer is precisely the main exploration direction of this combination therapy. The 'immune + anti-angiogenesis' combined with first-line and subsequent treatments of NSCLC under research globally have shown good anti-tumor activity and clinical application prospects.

On the basis of dual immune combination therapy (PD-1/PD-L1 inhibitors and CTLA-4 inhibitors), combined with anti-angiogenic drugs, it is expected to further improve the clinical efficacy. The combination of Ivonescimab and Cadonilimab with or without chemotherapy is expected to refresh the new efficacy record in the current field of NSCLC treatment.

In terms of safety, Cadonilimab specifically binds to the two targets of PD-1 and CTLA-4 with a short half-life, having good and controllable safety. Previous clinical trials have shown that Cadonilimab is significantly better than the CTLA-4 inhibitors on the market and is comparable to the PD-1/PD-L1 inhibitors on the market in overall safety. The current monotherapy clinical data of Ivonescimab also indicate that, perhaps due to the good local tumor targeting and the superiority of the bi-specific antibody structure, no obvious adverse reactions of bevacizumab have been observed, and its overall safety is better or comparable to that of PD-1/PD-L1 inhibitors currently on the market. Therefore, the safety of Ivonescimab combined with Cadonilimab is expected to be better or comparable to that of other PD-1/PD-L1 inhibitors combined with anti-angiogenic drugs.