Aduro Presents Preclinical Data for Anti-APRIL Antibody BION-1301 for the Treatment of IgA Nephropathy at ASN Kidney Week 2018
- Category: Antibodies
- Published on Sunday, 28 October 2018 14:55
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BERKELEY, CA, USA I October 26, 2018 I Aduro Biotech, Inc. (NASDAQ: ADRO) today announced preclinical data for its first-in-class anti-APRIL antibody BION-1301 supporting its use in the treatment of IgA nephropathy (IgAN) at the American Society of Nephrology (ASN) Kidney Week 2018 in San Diego, CA. IgAN is a progressive kidney disease characterized by an autoimmune antibody response against endogenous IgA. Preclinical studies demonstrated that BION-1301 binds to a specifically defined epitope on APRIL, resulting in complete blockade of APRIL induced receptor activation, and is expected to lead to suppression of IgA and the autoimmune response to IgA associated with the disease. Dosing of BION-1301 in non-human primates led to a significant reduction of blood IgA levels and established a favorable safety profile.
“Based on strong scientific rationale, BION-1301 is currently being evaluated in a Phase 1/2 clinical study for the treatment of multiple myeloma. The preclinical data presented today further indicate BION-1301’s potential in the treatment of IgAN,” stated Andrea van Elsas, Ph.D., chief scientific officer of Aduro. “Chronic exposure to BION-1301 was shown to significantly reduce serum IgA levels in non-human primates, suggesting this novel antibody may be instrumental in the reduction of IgA immune complexes deposited in the kidneys of patients with IgAN. We look forward to advancing the development of BION-1301 for this progressive kidney disease for which there currently is no approved therapy with curative intent.”
The abstract, “BION-1301: A Novel Fully Blocking APRIL Antibody for the Treatment of IgA Nephropathy,” was presented in a poster session titled “Molecular Mechanisms of CKD - II” and is available online at the ASN Kidney Week 2018 website.
IgAN, commonly referred to as Berger’s disease, is a progressive kidney disease characterized by an autoimmune antibody response against endogenous IgA. This results in local inflammation impeding kidney function, which may eventually lead to end-stage renal disease and the need for renal transplant. While IgAN has unclear causality and lacks approved disease-modifying options for therapy, preclinical data indicate that suppressing serum IgA and the anti-IgA autoimmune response by a neutralizing APRIL antibody, such as BION-1301, may reduce the progression and severity of proteinuria and other symptoms.
APRIL (a proliferation-inducing ligand) 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 multiple myeloma (MM) and binds to B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (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.
Aduro is currently evaluating BION-1301, its most advanced proprietary B-select monoclonal antibody, as a novel therapy for MM. Despite new treatments recently approved in MM, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. In preclinical studies, Aduro has established that 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. BION-1301 is currently being evaluated in a Phase 1/2 clinical study in patients with relapsed or refractory MM.
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 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-PD1 immune checkpoint inhibitor. 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