Deciphering the Potential of BION-1301: A Revolutionary APRIL Antibody in Combating Multiple Myeloma

APRIL (TNFSF13) is a ligand for BCMA and TACI receptors and has been linked to poor prognosis in multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and colorectal carcinoma due to elevated serum levels. An anti-APRIL antibody has been shown to impede CLL survival and reduce mouse B1 hyperplasia. APRIL is produced in the bone marrow and is known to trigger BCMA, promoting the proliferation and survival of MM cells. It also induces resistance to common treatments and encourages an immunosuppressive phenotype in BCMA+ cells.

A novel humanized anti-APRIL antibody, BION-1301, has been developed, initially discovered as hAPRIL.01A and later enhanced for stability. BION-1301 binds to human APRIL with high affinity and fully blocks the binding site for BCMA and TACI, as shown by its epitope mapping. This antibody effectively suppresses APRIL-induced B-cell IgA and IgG class switching and inhibits T cell-independent B cell responses in vivo.

BION-1301 has demonstrated the ability to neutralize APRIL, which can counteract MM survival, resistance, and the immunosuppressive phenotype. The antibody's mechanism of action and anti-tumor activity support its potential development as a standalone therapy or in combination with drugs like lenalidomib, bortezomib, and checkpoint inhibitors.

To facilitate clinical development, quantitative assays have been established to reliably quantify APRIL in human blood samples, overcoming limitations of previous assays. BION-1301 is anticipated to enter clinical development, with the potential to offer a new treatment approach for MM and possibly other B-cell related conditions.