China’s regulatory agency has approved the launch of Generon‘s Phase 1 clinical trial to test its immunotherapy candidate, A-319, in patients with acute lymphoblastic leukemia (ALL) and B-cell lymphoma.
Approval of Generon’s investigational new drug application for A-319 by China’s State Food and Drug Administration (SFDA) paves the way for the company to begin clinical testing of the therapy.
A-319 is an antibody that binds to two targets at the same time: the CD19 protein, highly present at the surface of healthy B-cells and many leukemia and lymphoma cells, and the CD3 protein, found on a large group of T-cells.
By binding both proteins simultaneously, A-319 creates a link between malignant cells and T-cells, leading to T-cell activation and the release of molecules that kill tumor cells. The antibody can also drive the expansion of T-cells.
A-319 follows the same principle used in other therapies directed against the CD19 protein, but is thought to be safer than other approaches. It was designed using Generon’s immunotherapy antibody technology platform called ITab, which produces human antibodies that target two molecules instead of one.
“Initiation of a Phase I study for A-319 in China is one of Generon’s goals this year. A-319 has a similar mechanism of action to eliminate malignant B cells to those of CAR-T and other CD19/CD3 bispecific antibodies, but it is more convenient for patient dosing and potentially with better safety,” Xiao Qiang Yan, PhD, CEO and chief scientific officer of Generon, said in a press release.
“Obtaining the SFDA’s approval for the A-319 Phase I trial is a significant accomplishment for Generon’s ITab platform. The [investigational new drug] approval is another step in demonstrating Generon’s innovative capabilities,” said Mi Jian Qing, professor at Ruijin Hospital, Shanghai Jiaotong University.
A-319 is Generon’s second T-cell-activating antibody to enter clinical trial testing. The first, A-337, is designed to bind T-cells and the cancer cell surface protein, EpCAm. In 2017, the therapy entered a Phase 1 trial for advanced solid tumors in Australia.
“A-319 is our second T-cell activating bispecific antibody to enter clinical development. Generon is expanding its ITab pipeline for both liquid and solid tumors and committed to bringing innovative immune-oncology antibodies to cancer patients in China and the world,” Yan said.