Aduro Biotech Reports Publishing of Key Preclinical Data Highlighting New Approach to Treat Multiple Myeloma

Aduro Biotech, Inc. ADRO today announced the publication of a pivotal paper elucidating the roles of B cell maturation antigen (BCMA) and its ligand A PRoliferation-Inducing Ligand (APRIL) in multiple myeloma, highlighting the potential of its proprietary monoclonal antibody (mAb) BION-1301 targeting APRIL. The authors demonstrated through in vivo and in vitro preclinical studies that the APRIL/BCMA ligand/receptor pair drives multiple myeloma tumor growth and survival, and activates immunosuppressive mechanisms that allow the tumor to thrive. Importantly, the studies demonstrated that BION-1301 halts tumor growth and overcomes drug resistance to chemotherapeutic agents lenalidomide and bortezomib in preclinical models. The study, entitled "APRIL and BCMA promote human multiple myeloma growth, chemoresistance, and immunosuppression in the bone marrow microenvironment," was published by Kenneth Anderson, M.D. Ph.D., and Yu-Tzu Tai, Ph.D. of the Dana-Farber Cancer Institute. The article appears online ahead of print in the peer-reviewed journal Blood. "For the first time, we have identified several different molecular mechanisms by which APRIL activates BCMA to promote multiple myeloma progression in vivo," said Dr. Anderson, program director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at Dana-Farber and Kraft Family Professor of Medicine at Harvard Medical School. "Understanding the mechanism of tumor progression and resistance allowed us to test a novel approach to potentially combat disease advancement by using an anti-APRIL antibody. BION-1301 blocks the APRIL-induced signal cascade at a critical juncture, and represents a new potential mechanism to both achieve disease response and restore immune function, even in patients with myeloma resistant to current therapies." The researchers also identified a novel and important role for APRIL and BCMA to induce immune suppression in multiple myeloma. They further developed a comprehensive understanding of APRIL as a strong driver of multiple features of tumor development even in the presence of protective bone marrow myeloid cells such as osteoclasts, macrophages, and dendritic cells. In contrast, introducing an anti-APRIL mAb blocked interaction with both BCMA and a second TNF receptor TACI to inhibit multiple myeloma tumor growth, adhesion to bone marrow cells and immune suppression. In addition, the introduction of BION-1301 allowed tumor cells to be susceptible to standard chemotherapy regimens of lenalidomide and bortezomib. "Current therapies for patients with multiple myeloma have significantly improved patient survival, however a need for new treatments exists as drug resistance develops in the majority of the cases," said Andrea van Elsas, Ph.D., chief scientific officer of Aduro Biotech Europe. "With the recent elucidation of the important role of the tumor microenvironment, we believe that blocking APRIL using our proprietary monoclonal anti-APRIL antibody BION-1301 could allow for a highly targeted immunotherapy approach to treat multiple myeloma, particularly when added to standard of care chemotherapy. Based on these promising preclinical data, we intend to initiate a clinical trial of BION-1301 next year."