On July 5, 2023 I-Mab (the "Company") (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of pioneering immunotherapies, reported the publication of a manuscript entitled "CLDN18.2 and 4-1BB bispecific antibody givastomig exerts antitumor activity through CLDN18.2-expressing tumor-directed T-cell activation" in the latest issue of The Journal for Immuno-Therapy of Cancer (JITC) (Press release, I-Mab Biopharma, JUL 5, 2023, View Source [SID1234633066]).

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Givastomig is engineered to bind to CLDN18.2-expressing cancer cells and co-stimulatory receptor 4-1BB on adjacent T cells, with the aim of activating T cells specifically within CLDN18.2-expressing tumors and triggering a potent tumor-killing effect. This innovative approach offers the potential for effective and targeted immuno-therapy in gastric cancer, a disease characterized by a poor prognosis and limited treatment options.

Results from this study demonstrated that 4-1BB+ T cells co-exist in close proximity to CLDN18.2+ gastric cancer cells in patients. Moreover, givastomig bound to tumor cells across a wide range of CLDN18.2 expression levels and induced 4-1BB activation only in the context of CLDN18.2 binding, indicating the targeted effect of 4-1BB activation in the presence of CLDN18.2+ cells. In the in vivo CLDN18.2-expressing tumor model, givastomig induces localized immune activation in tumors, increasing the ratio of CD8+/Treg cells, resulting in superior anti-tumor activity and long-lasting memory response against tumor rechallenge.

"The findings from our research demonstrate the significant potential of givastomig in treating gastric cancer patients with varying levels of CLDN18.2 expression," said Dr. Lin Shen, Professor of Clinical Oncology at the Beijing Cancer Hospital of Peking University, and Director of SIP LifeLink Oncology Research Institute. "By activating 4-1BB signaling in a CLDN18.2 engagement-dependent manner, givastomig can avoid the risk of liver toxicity and systemic immune response commonly observed with other 4-1BB stimulating agents in previous clinical trials."

"We are excited to see this manuscript published in JITC, as it showcases the innovative design and remarkable anti-tumor activity in preclinical models of givastomig," said Dr. Andrew Zhu, President of I-Mab. "This molecule has demonstrated promising results in this study by effectively activating T cells and triggering a localized immune response within the tumor microenvironment. With ongoing clinical studies, we aim to build upon these findings and ultimately make this innovative therapy accessible to patients with gastric cancer."

Givastomig is currently undergoing Phase 1 clinical studies both in the U.S. and in China. Encouragingly, the Phase 1 study has shown favorable safety profile and promising efficacy signals thus far. The Company intends to report additional clinical data from the study at a major medical conference in the second half of the year.

About Givastomig

Givastomig, also known as TJ-CD4B/ABL111, is a Claudin 18.2 and 4-1BB bispecific antibody capable of binding to tumor cells expressing Claudin 18.2, i.e., gastric cancer and pancreatic cancer cells, and stimulating intra-tumoral T cells by the 4-1BB arm designed to be activated only upon tumor engagement while silent elsewhere. Givastomig effectively maintains a strong tumor binding property and anti-tumor activity attributable to a synergistic effect of both Claudin 18.2 antibody and 4-1BB antibody while avoiding or minimizing liver toxicity and systemic immunotoxicity commonly seen with 4-1BB antibodies as a drug class. Being developed under collaboration between I-Mab and ABL Bio, a clinical-stage biotechnology company in South Korea, givastomig is currently being investigated in a phase 1 clinical study in the U.S. and China. In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for givastomig for the treatment of gastric cancer, including cancer of gastroesophageal junction.