Aduro Biotech and Dana-Farber Cancer Institute Present Preclinical Data Supporting Anti-APRIL Antibody BION-1301 for the Treatment of Multiple Myeloma at the 60th American Society of Hematology Annual Meeting and Exposition
- Category: Antibodies
- Published on Tuesday, 04 December 2018 10:00
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BERKELEY, CA, USA I December 03, 2018 I Aduro Biotech, Inc. (NASDAQ: ADRO) today announced preclinical data in two abstracts for its first-in-class anti-APRIL antibody BION-1301 supporting its potential use as a treatment for multiple myeloma (MM) at the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA. Data from the studies demonstrated that therapies blocking a proliferation inducing ligand (APRIL) from binding to B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI) may simultaneously target MM cells and APRIL-induced immunosuppression.
“Our newest findings from the data presented at ASH indicate that combining an anti-APRIL antibody such as BION-1301, which inhibits APRIL binding to TACI and BCMA, with a BCMA-targeted therapy may have the potential to augment anti-myeloma activity,” commented Dr. Kenneth C. Anderson, director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute. “These studies support the rationale for use of the investigational agent, BION-1301, in the treatment of multiple myeloma.”
Moreover, studies showed patient serum levels of APRIL were elevated at all stages of MM investigated, suggesting a role for APRIL in early development and pathogenesis. In addition, APRIL was found to induce production of key chemokines with osteolytic capacity. Blocking APRIL could modulate the tumor microenvironment more broadly, illustrating the potential of BION-1301 as a therapeutic agent for MM, particularly in combination therapies.
“We are encouraged by the data we presented at ASH, which support our ongoing clinical evaluation of BION-1301,” said Andrea van Elsas, Ph.D., chief scientific officer of Aduro. “We believe BION-1301 could represent a first-in-class therapy for the treatment of multiple myeloma and that its differentiated approach to blocking APRIL may have further potential in combination strategies.”
Aduro is currently conducting a Phase 1/2 multi-center, open-label study (see www.clinicaltrials.gov, identifier NCT03340883) designed to evaluate the safety and activity of BION-1301 in patients with relapsed or refractory MM whose disease has progressed after at least 3 prior systemic therapies, including immunomodulatory drugs, proteasome inhibitors, chemotherapies, or monoclonal antibodies.
The abstract, “APRIL Is Significantly Elevated at All Stages of Multiple Myeloma (MM) and Interferes with Anti-BCMA Monoclonal Antibody-Mediated Cytolysis, Supporting the Clinical Evaluation of BION-1301 As a Novel Therapeutic Approach in MM,” was presented in a poster session titled “652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster II” and is available online at the ASH Annual Meeting Website.
The abstract, “BION-1301 Blocks APRIL-Induced Anti-Apoptotic Signaling, Immune Suppressive Phenotype, and Chemokine Production Associated with Multiple Myeloma,” was presented in a poster session titled “651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster I” and is available online at the ASH Annual Meeting Website.
APRIL is a member of the tumor necrosis factor superfamily and is primarily secreted by bone marrow and/or myeloid cells. APRIL is overproduced in patients with MM and binds to BCMA and TACI to stimulate a wide variety of responses that promote MM growth and survival and suppress the immune system so that the tumor cells are protected and sustained in the bone marrow.
BION-1301 is currently being evaluated in a Phase 1/2 clinical study in patients with relapsed or refractory MM. Aduro also plans to explore BION-1301 as a potential treatment for IgA nephropathy (IgAN). Despite new treatments recently approved in MM, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. In prior preclinical studies, Aduro established APRIL plays a crucial part in the protective bone marrow tumor microenvironment. In these studies, APRIL, through BCMA, was shown to be critically involved in the survival, proliferation and chemoresistance of MM, 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. In addition, BION-1301 also demonstrated the ability to inhibit immune suppressive effects of regulatory T cells via TACI but not BCMA in MM blood and bone marrow.
Aduro Biotech, Inc. is an immunotherapy company focused on the discovery, development and commercialization of therapies that are intended to transform the treatment of challenging diseases. Aduro's technologies, which are designed to harness the body's natural immune system, are being investigated in cancer indications, autoimmune diseases and have the potential to expand into infectious diseases. Aduro's STING pathway activator technology is designed to activate the STING receptor in immune cells, which may result in a potent tumor-specific immune response. ADU-S100 (MIW815) is the first STING pathway activator compound to enter the clinic and is currently being evaluated in a Phase 1 clinical trial as a single agent and in combination with ipilimumab and in a Phase 1b combination trial with spartalizumab (PDR001), an investigational anti-PD-1 monoclonal antibody. Aduro’s B-select monoclonal antibody technology, including BION-1301, an anti-APRIL antibody, is comprised of a number of immune modulating assets in research and development. Aduro is collaborating with leading global pharmaceutical companies to expand its products and technologies. For more information, please visit www.aduro.com.
SOURCE: Aduro Biotech