BioAtla announced the U.S. Food and Drug Administration (FDA) has cleared BioAtla's Investigational New Drug application (IND) for BA3021, a first-in-class conditionally active ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC), in patients with solid tumors. Under this IND, the company intends to initiate a first-in-human, open label, multicenter, dose escalation and dose expansion study of CAB-ROR2-ADC in patients with locally advanced or metastatic solid tumors. CAB-ROR2-ADC will be BioAtla's second CAB investigational product to enter clinical trials in the United States with BioAtla initiating patient dosing in February of this year with CAB-AXL-ADC for treatment of solid tumors.
ROR2 is a developmentally restricted receptor tyrosine kinase (RTK) that interacts with Wnt ligands. Although essential for embryonic development, ROR2 expression is rare in normal adult tissues. Many of the activities associated with ROR2 in development have been implicated also in cancer including cell migration and invasiveness. ROR2 has been found to be overexpressed in multiple types of cancer including breast, renal, colorectal, melanoma, pancreatic, non-small cell lung cancer (NSCLC), and gastrointestinal stromal tumor (GIST). In general, ROR2 expression is associated with more aggressive disease states and poorer patient prognosis. Furthermore, recent studies by others indicate that overexpression of either ROR2 or AXL receptor is associated with resistance to anti-PD-1 therapy thereby suggesting immuno-oncology roles for BioAtla's first two clinical stage CAB candidates that target these receptors.
ROR2 is a cell surface Wnt5a receptor that is overexpressed in cancer cells making it an attractive target for therapy. BioAtla applies its proprietary CAB technology to develop its CAB antibody-drug conjugate (ADC) targeting ROR2 with the intent to activate binding to the ROR2 receptor in the tumor microenvironment and deliver the toxic payload only to the cancerous cells.