SUZHOU, China, July 15, 2021, Transcenta Holding Limited ("Transcenta"), a clinical stage global biotherapeutics company with fully-integrated capabilities in discovery, development and manufacturing of antibody-based therapeutics, announces that the first US patient has been dosed in the global Phase I clinical trial of PD-L1/TGF-β bi-functional antibody TST005.

TST005 is the second bi-functional anti-PD-L1 and TGF-β trap fusion protein entering the global clinical stage. It simultaneously targets two immuno-suppressive pathways, transforming growth factor -β (TGF-β) and programmed cell death ligand-1 (PD-L1), that are commonly used by cancer cells to evade the immune system. TST005 consists of a high affinity PD-L1 antibody fused with an engineered TGF-β Receptor Type II protein in its C-terminal. TST005 lacks FcR binding activity and thus has reduced FcR mediated killing of PD-L1 expressing effector T cells. TST005's high PD-L1 binding activity and enhanced TGF-β trap stability enables the targeted delivery of TGF-β trap into PD-L1 expressing tumors, thereby minimizing off-target toxicities of systemic inhibition of TGF-β signaling. TST005 displayed potent activity in vitro in reversing TGF-β induced T-cell suppression. In multiple syngeneic tumor models, TST005 induced significant increase of CD8 T-cell infiltration into PD-L1 expressing tumors and displayed dose-dependent tumor growth inhibition in tumor model not sensitive to PD-(L)1 treatment due to high level TGF-β. TST005 is well tolerated in non-human primates and displayed a linear PK profile. TST005 is a potential novel bi-functional immunotherapy candidate with improved therapeutic window.

"TST005 has potential application for the treatment of a large number of tumor types. It is expected to be effective in the patient populations who are either naïve or progressed after treatment with PD-(L)1 inhibitor." said Dr. Michael Shi, EVP, Head of Global R&D and CMO of Transcenta, "TST005 will be one of the company's key competitive products, considering that there are huge worldwide unmet needs in patients who failed checkpoint inhibitor therapies, by targeting PD-L1/TGF-β pathways."

"Primary and acquired resistance to immune checkpoint inhibitors represent a significant unmet need in cancer treatment." said Anthony W. Tolcher, M.D., FRCPC, FACP, Medical Oncologist, Co-founder of NEXT Oncology ™ and current study's investigator. "TST005 demonstrated potent antitumor efficacy in multiple pre-clinical models while maintaining wide safety margins, and I look forward to evaluating this novel bi-functional antibody in patients with advanced solid tumors."

This trial is a global Phase I trial with both US and China using the same protocol. Please refer to http://www.clinicaltrials.gov (NCT04958434) for additional information about this clinical trial.