Aduro Biotech Announces the Initiation of a Phase I/II Clinical Trial of BION-1301, a Novel Anti-APRIL Antibody, for the Treatment of Multiple Myeloma
-- Data Presented Recently at ASH Demonstrate BION-1301’s Blocking of TACI in Addition to BCMA Results in Inhibition of Regulatory T Cells --
BERKELEY, Calif., Dec. 18, 2017 (GLOBE NEWSWIRE) -- Aduro Biotech (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, today announced that the first patient in its Phase 1/2 dose escalation and dose expansion clinical trial (see www.clinicaltrials.gov, identifier NCT03340883) has been dosed at Virginia Cancer Specialists in Fairfax, Virginia, the first site in this multi-center trial. The study is designed to evaluate the safety and activity of BION-1301, a humanized anti-APRIL (A PRoliferation-Inducing Ligand) antibody, for adults with relapsed or refractory multiple myeloma.
“Neutralizing APRIL is a differentiated approach in the treatment of multiple myeloma, and it has been shown to inhibit tumor growth and overcome drug resistance in preclinical studies,” said Natalie Sacks, M.D., chief medical officer of Aduro Biotech. “BION-1301 is our wholly-owned novel antibody that has been shown in non-clinical studies to fully block the APRIL-induced signaling cascade at a critical juncture, and we are eager to further characterize its potential activity in the clinic. Until there is a cure for multiple myeloma which remains a debilitating disease, alternative treatments are needed.”
Recently, two datasets on anti-APRIL were presented at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia. Data presented by Yu-Tzu Tai, Ph.D., of the Dana Farber Cancer Institute in an oral session at ASH demonstrate that BION-1301 and its parental antibody blocked APRIL binding to both its receptors BCMA and TACI. Blocking APRIL with BION-1301 (or its parental antibody) not only inhibited proliferation and survival of multiple myeloma cells but it also alleviated drug resistance and immune suppression in preclinical models and cell culture, leading to enhanced anti-BCMA and daratumumab-mediated myeloma cell killing. Additionally, Dr. Tai and her colleagues demonstrated that regulatory T cells in the blood and bone marrow expressed TACI, and that APRIL blockade inhibited their function. Also, John Dulos, Ph.D., director and project team leader at Aduro Biotech, and his team conducted preclinical pharmacokinetic and pharmacodynamic studies indicating BION-1301 was well tolerated and binding of APRIL in preclinical models resulted in decreased IgA, IgG and IgM production in a dose-dependent fashion.
“We know that APRIL sets off a cascade of events that hinders the immune response to multiple myeloma cells, helping the disease escape immune attack. The data presented at ASH indicate that blocking APRIL by targeting BCMA alone may not be sufficient for the treatment of multiple myeloma, as APRIL critically modulates regulatory T cell function via TACI, not BCMA,” said Dr. Tai. “Importantly, BION-1301, as a fully-blocking monoclonal antibody, may have unique efficacy by inhibiting APRIL-induced proliferation of immune system components linked to multiple myeloma progression.”
About Phase 1/2 Trial
The Phase 1/2 multi-center, open-label study is designed to evaluate the safety and activity of BION-1301 in patients with relapsed or refractory multiple myeloma whose disease has progressed after at least 3 prior systemic therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors, chemotherapies, or monoclonal antibodies. The Phase 1 part of the study will evaluate the safety, pharmacokinetics and pharmacodynamics of escalating doses of BION-1301 administered once every two weeks in a 28-day cycle. Once the recommended Phase 2 dose is determined, the Phase 2 part of the study will begin. It will assess safety and preliminary activity of BION-1301 at the selected dose, with a primary activity endpoint of objective response rate.
About APRIL and BION-1301
APRIL (A PRoliferation-Inducing Ligand) is a member of the tumor necrosis factor (TNF) superfamily and is primarily secreted by bone marrow and/or myeloid cells. APRIL is overproduced in patients with multiple myeloma and binds to BCMA (B cell maturation antigen) and TACI (Transmembrane Activator and CAML Interactor) to stimulate a wide variety of responses that promote multiple myeloma growth and suppress the immune system so that the tumor cells are allowed to proliferate. BION-1301 is a humanized anti-APRIL antibody that has been shown in preclinical studies to effectively neutralize APRIL, eliminate malignant cells and reduce resistance to therapy in models of multiple myeloma. In addition to multiple myeloma, APRIL’s role in other cancers and in B cell dependent autoimmune and inflammatory diseases indicate that BION-1301 may also be useful in treating chronic lymphocytic leukemia, colorectal cancer and Berger’s disease (caused by IgA antibody deposits in the kidneys).
About Multiple Myeloma
Lymphocytes (B cells and T cells) are the primary cell types within the immune system that work together to fight infection and disease. As B cells respond to normal infection in the body, they mature and change into plasma cells, which in turn make antibodies that help the body attack infection. While lymphocytes circulate throughout the body, plasma cells remain primarily in the bone marrow. Multiple myeloma is a blood cancer that occurs when malignant plasma cells proliferate uncontrollably. Approximately 50,000 new cases of multiple myeloma are expected to be diagnosed in the United States and Europe each year. While many new therapies have become available in recent years, multiple myeloma remains incurable and significant unmet needs exist among patients who relapse following, are resistant to, or cannot tolerate currently available agents.
Aduro Biotech, Inc. is an immunotherapy company focused on the discovery, development and commercialization of therapies that transform the treatment of challenging diseases. Aduro's technology platforms, which are designed to harness the body's natural immune system, are being investigated in cancer indications and have the potential to expand into autoimmune and infectious diseases. Aduro's STING Pathway Activator platform is designed to activate the STING receptor in immune cells, resulting in a potent tumor-specific immune response. ADU-S100 is the first STING Pathway Activator compound to enter the clinic and is currently being evaluated in both a Phase 1 monotherapy study as well as a Phase 1b combination study with an anti-PD1 immune checkpoint inhibitor. Aduro’s B-select monoclonal antibody platform is comprised of a number of immune modulating assets in research and development, including BION-1301, an anti-APRIL antibody. Aduro's pLADD program is based on proprietary attenuated strains of Listeria that have been engineered to express tumor neoantigens that are specific to an individual patient’s tumor. Other Listeria strains for lung and prostate cancers are being advanced by a partner. Aduro is collaborating with leading global pharmaceutical companies to expand its products and technology platforms. For more information, please visit www.aduro.com.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding our intentions or current expectations concerning, among other things, the potential for BION-1301 and our technology platforms, our plans, the timing and availability of results of our clinical trials and those of our collaborators, and the potential for eventual regulatory approval of our product candidates. In some cases, you can identify these statements by forward-looking words such as “may,” “believe,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect,” “targeted” or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our history of net operating losses and uncertainty regarding our ability to achieve profitability, our ability to develop and commercialize our product candidates, our ability to use and expand our technology platforms to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, our reliance on third parties, and our ability to obtain and adequately protect intellectual property rights for our product candidates. We discuss many of these risks in greater detail under the heading “Risk Factors” contained in our quarterly report on Form 10-Q for the quarter ended September 30, 2017, which is on file with the Securities and Exchange Commission. Any forward-looking statements that we make in this press release speak only as of the date of this press release.
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