VLS-101 is an investigational antibody-drug conjugate (ADC) targeting cancers that commonly express receptor tyrosine kinase-like orphan receptor 1 (ROR1). VLS-101 comprises a humanized monoclonal antibody targeting ROR1, a proteolytically cleavable linker, and the anti-microtubule cytotoxin, monomethyl auristatin E (MMAE). The linker-toxin combination (known as vedotin) is already used in available ADCs that target other tumor antigens.
VLS-101 binds to ROR1-expressing tumor cells, resulting in internalization of the ADC-ROR1 complex. Within these tumor cells, lysosomal enzymes release the cytotoxin (ie, MMAE). Binding of MMAE to tubulin disrupts the microtubule network within the tumor cell, subsequently inducing cell-cycle arrest and apoptotic tumor cell death.
VLS-101 has demonstrated in vivo activity, including complete regression of tumors, in nonclinical models of hematologic malignancies and solid tumors.
A Phase 1, first-in-human clinical trial of VLS-101 monotherapy in patients with hematologic cancers is ongoing. Further details are available at ClinicalTrials.gov.
Next-Generation ROR1-directed Antibody-Drug Conjugates
VelosBio is evaluating next-generation, investigational antibody-drug conjugates (ADCs) by testing multiple combinations of stable conjugations, cleavable linkers, and payloads. The goal is to develop ROR1-targeted ADCs that are broadly active and well tolerated and that complement VLS-101 by offering alternative methods of potential tumor cell killing.
ROR1-directed Bispecific Antibodies
VelosBio is developing investigational ROR1-targeting bispecific antibodies (BiAbs) that are designed to harness the immune system to kill tumors. Anti-ROR1 BiAbs have been generated in multiple formats that bind to CD3 receptors on T cells or CD16 receptors on natural killer cells, thereby attracting these immune cells to destroy the cancer.