B-select Monoclonal Antibodies

Aduro’s B-select platform employs a proprietary ultra-selective functional screening process to identify antibodies with unique binding properties against a broad repertoire of targets that can modulate key targets in immuno-oncology.

The technology is based on in vitro clonal expansion of B cells (antibody-producing cells) isolated from the spleen or lymph nodes of immunized animals, capable of rescuing one of every two antigen-specific B cells induced in mice. This unprecedented efficiency enables exploration of the full repertoire of B cells induced to uncover unique antibodies with pre-specified function (the ‘needles in the haystack’) in validated and proprietary targets.

Using this platform, Aduro has developed a deep pipeline of preclinical monoclonal antibodies (B-select mAbs) that have the potential to regulate the immune system of patients with cancer. Aduro’s pipeline includes antagonists and checkpoint inhibitors, which are intended to activate the immune system by removing suppression – this is also known as “releasing the brakes” on the immune system. In addition, Aduro has developed agonists, which are unique antibodies that stimulate immune responses when cancer is not detected by the immune system. These mAbs are designed to be used alone or in combination with other therapies, including the LADD® and STING platforms to increase immunotherapy potency and durability.

Aduro plans to evaluate BION-1301, its most advanced proprietary B-select mAb, as a novel therapy for multiple myeloma. Despite new treatments recently approved in multiple myeloma, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. Aduro has established that A PRoliferation-Inducing Ligand (APRIL) plays a crucial part in the protective bone marrow tumor microenvironment. In preclinical studies, APRIL, through the B cell maturation antigen (BCMA), was shown to be critically involved in the survival, proliferation and chemoresistance of multiple myeloma, and upregulates mechanisms of immunoresistance, including PD-L1 upregulation. BION-1301, a humanized antibody that blocks APRIL from binding to its receptors, has been shown in preclinical studies to halt tumor growth and overcome drug resistance. A phase 1 clinical trial is planned for 2017.

Aduro’s second lead candidate is an anti-CD27 antibody being advanced by Merck under its collaboration agreement. CD27 has been recognized as having a critical role in activating a productive anti-cancer (CD8 T-cell) immune response and has demonstrated the potential to be combined with checkpoint inhibitors in pre-clinical studies. Aduro’s anti-CD27 antibody is distinct because it targets a functional epitope on CD27 which demonstrated potent activation of the CD27 co-stimulatory pathway in pre-clinical studies.