ISU Abxis

Nov 8, 2022

Nov. 8, 2022 Biocytogen Pharmaceuticals Co. Ltd. ’s subsidiary Eucure Biopharma Co. Ltd. has granted Isu Abxis Co. Ltd. rights to use its humanized agonistic anti-CD40 antibody YH-003 to develop cancer drugs. Isu Abxis will leverage the license to develop trispecific antibodies for several cancer indications, while Eucure will receive an up-front payment, milestone payments and royalties of unspecified value. “CD40 is a key co-stimulator in adaptive immune responses,” said Yeob Hwang, CEO of South Korea-based Isu Abxis. “We are glad for the opportunity to utilize Biocytogen/Eucure Biopharma’s anti-CD40 antibody YH-003, as it has outstanding efficacy and safety profiles, both preclinically and clinically.” CD40 is a member of the tumor necrosis factor receptor superfamily. It is an important co-stimulator expressed on the surface of immune cells, especially innate immune cells such as dendritic cells. Research has shown that CD40 activation is a key regulatory point for tumor immunotherapy, transforming cold tumors lacking immune cell infiltration into hot tumors that respond well to tumor immunotherapy. Biocytogen used its in vivo drug screening platform to develop YH-003. So far, a phase I trial has shown it to have “good tolerability and safety profiles, as well as encouraging antitumor activities against several tumor types, including malignant melanoma and pancreatic cancer,” said Rong Chen, vice president of Biocytogen and CEO and chief medical officer at Beijing-based Eucure. YH-003 is an agonistic antibody that specifically binds to CD40 to promote the antigen presentation process and thus positively regulate the anti-tumor T-cell responses. Eucure is conducting five clinical trials of the candidate in different solid tumors, according to a spokesperson for Biocytogen. “In the animal models, while the competitor CD40 antibody showed significant liver toxicity and cytokine release, YH-003 did not show liver enzyme elevation or cytokines release,” the spokesperson said. Eucure is running a phase II multicenter clinical trial of YH-003 in combination with anti-PD-1 monoclonal antibody toripalimab in subjects with unresectable/metastatic pancreatic ductal adenocarcinoma (PDAC) in Australia, the U.S. and China. Patients with confirmed progressive disease during treatment with first-line standard therapy were enrolled in the study. A phase I trial of YH-003 in combination with toripalimab in people with advanced solid tumors is also underway in Australia. The candidate is also being studied as a monotherapy in a multicenter, open-label phase I study to treat patients with advanced solid tumors in China. In addition, Eucure is running a phase II study of YH-003 in combination with pembrolizumab and albumin-bound paclitaxel in the first-line treatment of patients with unresectable/metastatic mucosal melanoma in China. The study completed initial patient dosing in July 2022. Finally, the company is also running a multicenter, open-label, phase I trial to evaluate YH-003 in combination with CTLA-4 mAb YH-001 and PD-1 pembrolizumab in subjects with advanced solid tumors in Australia and China. Besides YH-003, another asset in Eucure’s pipeline, YH-001 is currently in a phase II study for solid tumors, while anti-OX40 mAb YH-002 and anti-4-1BB mAb YH-004 are both in phase I trials. Seven other preclinical molecules will be soon moved to IND-stage, according to Biocytogen. In October 2022, Eucure Biopharma out-licensed YH-002 to Syncromune Inc. for the development of intratumoral immunotherapy. “For our preclinical assets generated from Project Integrum, the large-scale project to develop antibody drugs for more than 1,000 targets, we have reached 28 preclinical antibody drug co-development or license agreements with 16 pharmaceutical companies,” said Biocytogen. The company has developed five fully human antibody discovery platforms, which are designed for the discovery of monoclonal antibodies, bispecific antibodies, bispecific antibody-drug conjugates, T-cell receptor (TCR)-mimic antibodies and antibodies targeting G protein-coupled receptors (GPCRs). In September 2022, Biocytogen went public on the Hong Kong Stock Exchange, raising HK$471.1 million (US$60 million).