Ocean Biomedical and Aesther Healthcare Acquisition Corp. (Aesther) announced the discovery of bispecific antibodies that target Chitinase 3-like-1 and immune checkpoint inhibitors, killing glioblastoma cells and melanoma cells, and blocking the metastasis of malignant melanoma cells to the lung by over 90%. Glioblastoma multiforme (GBM) is a deadly type of brain tumor and 5- year survival is just 8% for those aged 45 to 54.

About 25% of GBM patients are not actively treated due to rapid disease progression. Malignant melanoma, the most serious skin cancer, can metastasize to other organs. Once it has spread to other organs it is difficult to treat.

Metastatic melanoma (Stage IV) has 22.5% five year survival. Non-small cell lung cancer (NSCLC) is a major unmet medical need that accounts for 85% of pulmonary malignancies and effects approximately 450,000 individuals. In greater than 50% of affected patients the tumors are diagnosed at advanced stages with metastatic spread that precludes curative surgical resection.

Background Recent studies of NSCLC have highlighted genetic abnormalities that underlie these tumors. These genetic abnormalities generate abnormal proteins that have not been previously seen by the patient's immune system which, in turn, activates antitumor immune responses that control tumor initiation and progression. Studies over recent years have demonstrated that tumor initiation and progression are often mediated by the ability of the tumors to produce immunosuppressive proteins and activate immunosuppressive pathways, called immune checkpoint inhibitors (ICPI), that allow tumor growth and progression by shutting off these critical anti-tumor immune responses.

This includes the programmed death (PD) pathway including PD-1, PD ligand 1 (PD-L1) and PD-L2 and the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) pathway that includes CTLA4 and its binding partners B7.1/B7.2. Antibodies that target ICPI such as PD-1, PD-L1 and CTLA4 have been generated which have therapeutic efficacy in NSCLC and other tumors. Unfortunately, only a minority of patients respond to these therapies and the responses are often not durable. Chitinase 3-like-1 (CHI3L1) is a member of the 18 glycosyl hydrolase gene family that is readily detected in the circulation of normal individuals and expressed at exaggerated levels in the circulation of individuals with diseases characterized by inflammation, tissue remodeling and or cancers.

Discoveries Recent studies from its laboratory have demonstrated that CHI3L1 is a critical regulator of a number of key cancer- causing pathways.