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Aduro Biotech and Dana-Farber Cancer Institute Publish Data Highlighting Immunosuppressive Impact of APRIL in Multiple Myeloma in Leukemia
BERKELEY, Calif., Sept. 04, 2018 (GLOBE NEWSWIRE) -- Aduro Biotech, Inc. (NASDAQ: ADRO) today announced the publication of a peer reviewed paper in Leukemia authored by scientists from the Dana Farber Cancer Institute and Aduro as part of their ongoing collaboration to study the role of APRIL (A PRoliferation Inducing Ligand) in multiple myeloma (MM). The authors profile the impact that APRIL, acting through its receptor TACI (transmembrane activator and cyclophilin ligand interactor), has on immune regulatory T cells (Tregs) in MM. The paper further reports that APRIL binding to TACI contributes to the immunosuppressive and treatment resistant MM bone marrow microenvironment, an effect that could potentially be mitigated by anti-APRIL antibody, BION-1301. Aduro is currently advancing BION-1301 in a Phase 1/2 dose escalation trial for the treatment of MM.
Key findings from the study include the observation that TACI expression is significantly higher in Tregs than conventional T cells from the same patient. APRIL significantly stimulates proliferation and survival of these Tregs, whereas a neutralizing anti-APRIL antibody (BION-1301) may inhibit these effects. Furthermore, the paper explained how APRIL specifically augments Tregs to enhance MM cell survival.
“It is now well-known that APRIL acts through its two receptors TACI and BCMA (B cell maturation antigen), the most specific MM antigen expressed at high levels in malignant plasma cells/B cells of all MM patients. Our newest findings from this study indicate that an anti-APRIL antibody such as BION-1301 may have the potential to treat MM through a differentiated mechanism of action, not only by inhibiting APRIL binding to BCMA, but also stimulating immunity to cancer by blocking APRIL binding to TACI,” commented Dr. Yu-Tzu Tai, lead author and Principal Scientist in Medical Oncology at the Dana-Farber Cancer Institute.
The paper entitled “APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: therapeutic implications,” can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/30135465.
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 multiple myeloma 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.
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 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, 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-PD1 immune checkpoint inhibitor. Aduro’s B-select monoclonal antibody platform, including BION-1301, an anti-APRIL antibody, is comprised of a number of immune modulating assets in research and development. 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 ability to advance our drug development programs. In some cases you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” 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 June 30, 2018, which is on file with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
|Jennifer Lew||Aljanae Reynolds|
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