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December 19, 2019

BeyondSpring Publishes Report on Benefits and Mechanism of Plinabulin in Reducing Neutropenia with Multiple Chemotherapies

Plinabulin Protects Bone Marrow from Chemotherapy-Induced Deficiencies with a Differentiated Yet Complimentary Mechanism to G-CSF for CIN Prevention

NEW YORK, Dec. 19, 2019 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies, today announced that the peer reviewed journal Cancer Chemotherapy and Pharmacology published a report on the unique mechanism of action (MoA) of the Company’s lead asset, Plinabulin. The report demonstrates that Plinabulin can successfully treat chemotherapy-induced neutropenia (CIN) caused by multiple chemotherapies. In addition, Plinabulin has positive effects on bone marrow cells, with a mechanism distinct from G-CSF-based therapies, the current standard of care for CIN.

The paper, titled, “Plinabulin ameliorates neutropenia induced by multiple chemotherapies through a mechanism distinct from G‑CSF therapies,” reports on Plinabulin’s ability to reduce neutropenia induced by docetaxel, cyclophosphamide or doxorubicin chemotherapy, without affecting bone marrow or blood G-CSF levels. The results support Plinabulin’s clinical testing as a non-G-CSF-based treatment for CIN associated with chemotherapies of different mechanisms.

“Importantly, our nonclinical data also demonstrated the positive effects of Plinabulin on bone marrow cells—consistent with clinical results recently reported in human subjects at ASH 2019—which demonstrate that Plinabulin increases the number of circulating white blood cells positive for CD34 (a marker for hematopoietic stem and progenitor cells, or HSPC, in humans), as well as the finding that Plinabulin protects bone marrow lymphoid and myeloid progenitor cells from the negative effects of chemotherapy,” said James R. Tonra, Senior Vice President, Preclinical Development at BeyondSpring and the lead author of the article. “A therapy that increases bone marrow HSPC count also has the potential to alleviate chemotherapy-induced deficiencies (chemo-assault) in multiple mature cell populations within the hematopoietic system. In line with this potential, Plinabulin alleviates docetaxel-induced thrombocytopenia, as well as neutropenia, in NSCLC patients.”

“By combining these two molecules – Plinabulin and G-CSF – patients get the benefit of these different and additive mechanisms of action that can work together to create a new standard of care in preventing CIN,” added Dr. Ramon Mohanlal, BeyondSpring’s Chief Medical Officer and Executive Vice President, Research and Development. “CIN not only puts chemotherapy patients at increased risk of infections and mortality, but also can deny them from receiving the best anti-cancer care, as CIN typically leads to a decrease / delay or discontinuation of otherwise effective chemotherapy. A chemotherapy dose reduction of just 15 percent can reduce long-term survival by as much as 50 percent. Plinabulin has also demonstrated anti-cancer activity in studies to date, and the addition of Plinabulin to G-CSF potentially offers the distinct advantage of better protection against CIN versus G-CSF alone, avoidance of G-CSF-related bone pain and improving outcomes.”

The article is authored by BeyondSpring’s James Tonra, Ph.D.; Ramon Mohanlal, MD, Ph.D.; G. Kenneth Lloyd, Ph.D., Chief Scientific Officer; and Lan Huang, Ph.D., Co-Founder, Chairman and CEO.

About BeyondSpring
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 two Phase 3 global clinical programs, one as a direct anticancer agent in the treatment of non-small cell lung cancer (NSCLC) and the other in the prevention of chemotherapy-induced neutropenia (CIN). BeyondSpring has strong R&D capabilities with a robust pipeline in addition to Plinabulin, including three immuno-oncology assets and a drug discovery platform using the ubiquitination degradation pathway. The Company also has a seasoned management team with many years of experience bringing drugs to the global market.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a marine-derived small molecule that sequesters tubulin heterodimers in a differentiated manner from other agents in this class. Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia (CIN). The anticancer benefits of 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. Plinabulin’s CIN data highlights the ability to boost the number of hematopoietic stem / progenitor cells (HSPCs), or lineage-/cKit+/Sca1+ (LSK) cells in mice. Effects on HSPCs could explain the ability of Plinabulin to not only treat CIN but also to reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients.

About Chemotherapy-Induced Neutropenia (CIN)
CIN is a common, often severe side effect that cancer patients who are undergoing treatment experience involving the destruction of neutrophils, which are a type of white blood cell and a patient’s first line of defense against infections. The current standard of care for CIN prevention is G-CSF monotherapy, which has serious limitations as described in its product information summary.

As many as 90 percent of patients who receive high-risk chemotherapy and G-CSF monotherapy may still experience grade 3 or 4 neutropenia [Lee et al., Annals of Surgical treatment and research 94(5): 223-228 (2018)]. Patients with grade 4 (severe) neutropenia have an abnormally low concentration of neutrophils, making these patients more susceptible to bacterial / fungal infections and sepsis, which can require hospitalization and be fatal. Grade 4 CIN can have an adverse effect on chemotherapy administration and is usually considered a significant predictor of low relative dose intensity (RDI), dose delays and dose reductions [Lalami Y, Critical Reviews in Oncology / Hematology, 120: 163 – 179 (2017)]. Even a 15 percent chemotherapy dose reduction can reduce long-term survival by as much as 50 percent [Bonadonna, Med Oncol 29:1495–1501 (2012)].

Additionally, as many as 70 percent of patients using G-CSF monotherapy experience bone pain [Moore et al., Annals of Pharmacotherapy 51(9): 797-803 (2017)]. Twenty-five percent of patients also report that the pain is severe. The National Comprehensive Cancer Network (NCCN) guidelines require that patients with grade 3 or 4 neutropenia decrease chemotherapy dose intensity, delay chemotherapy cycle timing or discontinue chemotherapy, each of which can have a negative effect on the long-term outcomes of cancer care [Lalami et al., Critical Reviews in Oncology / Hematology 120: 163-179 (2017)].

Cautionary Note Regarding Forward-Looking Statements
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,” “potential,” “suggest,” “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. Certain of the statements made in this press release are forward-looking, such as those, among others, relating to BeyondSpring’s expectations regarding the completion of the proposed offering. No assurance can be given that the offering discussed above will be consummated, or that the net proceeds of the offering will be used as indicated. Consummation of the offering and the application of the net proceeds of the offering are subject to numerous possible events, factors and conditions, many of which are beyond the control of the Company and not all of which are known to it, including, without limitation, market conditions and those described under the heading “Risk Factors” in the Company's Annual Report on Form 20-F for the year ended December 31, 2018, as updated by those risk factors included in the Company’s subsequent filings under the Securities Exchange Act of 1934, as amended, which can be accessed at the SEC's website at www.sec.gov. 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, the anticipated amount needed to finance the Company’s future operations, unexpected results of clinical trials, delays or denial in regulatory approval process, its expectations regarding the potential safety, efficacy or clinical utility of its product candidates, or additional competition in the market, and other risk factors referred to in BeyondSpring’s current Form 20-F on file with the SEC. The 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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