SHANGHAI--(BUSINESS WIRE)--December 3rd, 2018, Shanghai, Generon BioMed Holding Ltd (Generon), announced today at the American Society of Hematology (ASH) Annual Meeting the pre-clinical study results of two novel immunotherapies, A-319 (mono-valent) and A-329 (bi-valent), two CD19×CD3 bi-specific antibodies designed using Generon’s ITab™ platform. A series of studies were conducted to evaluate the bioactivities of A-319 and A-329 in vitro and in vivo. The in vitro data showed that the mono-valent and bi-valent CD19 binding had little effect on the CD3-associated activities including CD3 antigen binding affinity, T cell binding, and T cell activation. In contrast, the bi-valent binding format of A-329 showed better potency compared to the mono-valent format of A-319 in CD19 binding (KD 0.89 nM and 19.4 nM respectively) and in vitro human B cell killing (EC50 0.2 pM and 3.4 pM, respectively). Both A-319 and A-329 were capable of mediating tumor cell lysis with EC50 at 0.03~4.0 pM. A-329 demonstrated a greater killing activity on B cell lines with a low expression of CD19 antigen. In addition, The CD19 bi-valent format of A-329 revealed more B cell killing in monkeys. No significant differences of cytokine induction or liver injuries between A-319 and A-329 were observed. In human PBMC engrafted mouse models, in vivo efficacies of both formats on inhibiting tumor growth or improving animal survival rate were also confirmed. These results demonstrated that both A-319 and A-329 may benefit patients with B cell malignancies with less frequent dosing and lower levels of cytokine inductions than comparator therapies. A-329 especially has the potential to eliminate low CD19 expressing tumor stem cells.
Dr. David Lacey, chairman of Generon’s scientific advisory board, commented, “The prosecution of A-319 and A-329 ITabs targeting underscores the broadening of Generon’s portfolio into the immune-oncology space. The inherent flexibility of the ITab design and the competitive attributes of its manufacture make this bi-specific platform particularly attractive for CD19 as well as future targets.”
Dr. Xiao Qiang Yan, CEO and CSO of Generon, commented, “Targeting CD19 to treat patients with B cell malignancies remains a substantial unmet medical need. Generon has been focusing on developing CD3-activating bi-specific ITabs with the goal to serve patients better through more convenient dosing, improved efficacy and reduced side-effects. The preclinical data suggest that A-319 and A-329 may have unique advantages over other technologies or therapies targeting CD19”.
About A-319 and A-329
A-319 and A-329 are T cell activating bi-specific antibodies (BsAb) designed to target CD19 and CD3 (anti-CD19, anti-CD3) and are under development for the treatment of patients with B cell malignancies including B cell leukemia and B cell lymphoma. Both A-319 and A-329 activate T lymphocytes in a patient to kill CD19 expressing malignant B-cells, and A-329 may also activate T lymphocytes in a patient to kill low CD19 expressing malignant B cells. A-319 was recently approved by SFDA to initiate a phase I study in patients with B cell malignancies in China.
About Generon Corporation
Generon BioMed Holding Ltd is a privately held and leading biotechnology company located in Shanghai, China focusing on the development of innovative biological therapies for patients worldwide. It is the therapeutic biologics division of its parent company, Yifan pharmaceuticals.