Promising New Immuno-Oncology Component to Plinabulin’s Mechanism-of-Action to be Presented at 2019 American Association for Cancer Research Annual Meeting
NEW YORK, March 26, 2019 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, announced today that the Company will present a promising new strategy for cancer treatment involving the ability of lead asset, Plinabulin, to positively shift the balance of macrophage phenotypes for beneficial anti-cancer effect at the 2019 American Association for Cancer Research (AACR) Annual Meeting in Atlanta, Georgia. The results will be highlighted in a poster presentation titled, “Microtubule Destabilization by Plinabulin Generates Anti-Tumor Immune Response through Repolarization of Intratumoral Macrophages,” taking place on April 3rd from 8 a.m. to 12 p.m. local time.
Tumor-associated macrophages are believed to play an important role in the growth, progression and metastasis of tumors. While macrophages with an M1 phenotype have anti-cancer functions, M2 macrophages are thought to support tumor cell survival and metastasis. Having the ability to increase M1 and/or reduce M2 macrophages may help the immune system to slow the growth of tumors or reject tumors. Collaborators of BeyondSpring at the University of Basel demonstrated that Plinabulin not only reduced tumor-associated M2 macrophages in a murine cancer model, but also shifted the phenotypic balance to one favoring M1 macrophages. Moreover, Plinabulin treatment shifted the M1/M2 balance towards M1 for human donor cells in vitro.
“The effects of targeting microtubules varies in different cell types,” said Dr. James Tonra, Senior Vice President, Preclinical Development at BeyondSpring. “For an agent like Plinabulin that targets microtubules in a differentiated manner, it is therefore important to characterize the effects of Plinabulin in different models and cell systems to fully understand the mechanisms underlying the benefits observed to date in the clinic. The work performed by Dr. Alfred Zippelius (Lab Head Cancer Immunology) and Dr Abhishek Kashyap (Project Head) at the University Hospital of Basel indicates that effects on tumor associated macrophages may contribute towards these benefits.”
Dr. Zippelius and Dr Kashyap from the University of Basel added, “We observed potent effects of Plinabulin on tumor associated macrophages. We noted direct effects of Plinabulin on tumor resident as well as ex vivo cultured macrophages where Plinabulin induced functional M1 polarization of the macrophages accompanied by increased production and release of pro-inflammatory cytokines namely IL-1b, IL-6 and IL-12. Such M1 polarization may lead to pro-inflammatory reprogramming of the tumor microenvironment that supports T cell infiltration and anti-tumor immunity. We are directing our future efforts at gaining further insights into this mode of action of Plinabulin and at defining the right immunotherapeutic combination partner for pre-clinical validation.”
“Shifting the M1/M2 ratio to a predominant M1 phenotype can shift the balance from an immune-suppressive to an immune-enhancing tumor microenvironment (TME). Checkpoint inhibitors (PD1/PD-L1- and CTLA4-inhibitors), although very effective, over time often lose their efficacy due to resistance development. Tumor-associated macrophages (TAMs) of the M2 phenotype contribute to an immune-suppressive TME that may induce resistance to checkpoint inhibitor therapy. The finding of Plinabulin’s ability to improve the M1/M2 balance, along with the prior demonstration of increased dendritic cell maturation with Plinabulin treatment, support the potential utility of adding Plinabulin to established checkpoint-inhibitor therapy to increase potency, and to potentially reverse resistance to these checkpoint inhibitors. Early stage clinical trials are underway to test these new strategies,” added Dr. Ramon Mohanlal, Executive Vice President of R&D and Chief Medical Officer, BeyondSpring.
The AACR Annual Meeting will take place from March 29 through April 3, 2019, at the Georgia World Congress Center in Atlanta. BeyondSpring’s abstract can be found on the AACR conference website here.
Plinabulin, a marine-derived small-molecule that sequesters tubulin heterodimers in a manner differentiated from other agents in this class, is BeyondSpring’s lead asset. Following positive Phase 2 results, Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia. Plinabulin reduced chemotherapy-induced neutropenia in association with reduced thrombocytopenia and increased circulating CD34+ progenitor cell mobilization in patients. Studies of Plinabulin's mechanism of action in animals indicate that these broad effects on the hematopoietic system may relate to positive effects on hematopoietic stem / progenitor cells in the bone marrow, with increased tissue cytokine / IL-6 secretion. The anticancer benefits of targeting tubulin / microtubules with Plinabulin have been associated with positive effects on antigen presenting cells and T-cell activation, as well as to the direct killing of cancer cells.
BeyondSpring is a global, clinical-stage biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies. BeyondSpring’s lead asset, Plinabulin, is in a Phase 3 global clinical trial as a direct anticancer agent in the treatment of non-small cell lung cancer and two Phase 2/3 clinical programs in the prevention of chemotherapy-induced neutropenia. BeyondSpring has internal R&D capabilities with a robust pipeline including, in addition to Plinabulin, three immuno-oncology assets and a drug discovery platform using ubiquitination degradation pathway. The Company has a seasoned management team with many years of experience bringing drugs to the global market.
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This press release includes forward-looking statements that are not historical facts. Words such as "will," "expect," "anticipate," "plan," "believe," "design," "may," "future," "estimate," "predict," "objective," "goal," or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring's current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company's future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet our expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSpring’s most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law.
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