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Nov 08,2018
Clinical Results for BeyondSpring’s Lead Asset, Plinabulin for the Prevention of Chemotherapy-Induced Neutropenia, Demonstrated Superior Immune Profile Compared to Neulasta®

Company to Present Latest Findings at 2018 Society for Immunotherapy of Cancer’s (SITC) Annual Meeting

NEW YORK, Nov. 08, 2018 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today reported new data from its clinical program for Plinabulin, which demonstrated a superior immune profile compared to Neulasta (pegfilgrastim) based on promyelocytes and immature neutrophil data from clinical study.  The data will be presented by Dr. Douglas Blayney, global Principal Investigator for BeyondSpring’s CIN development program and Professor of Medicine at Stanford University Medical Center, in a poster presentation titled, “Pegfilgrastim, but not Plinabulin, generates a blood myeloid cell (BMC) repertoire with a predominant immunosuppressive phenotype,” at the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting.

The data showed that, Neulasta induced a peripheral blood immune profile that is known to potentially increase immune suppression. In contrast, Plinabulin did not generate this predominant immunosuppressive phenotype. Neulasta, a long-acting G-CSF and the current standard of care for chemotherapy-induced neutropenia (CIN), is believed to activate the bone marrow, resulting in an overproduction of neutrophils. Clinical data suggest that a large proportion of these neutrophils appear to represent immature neutrophils, which typically make their way to the tumor tissue, and tip the immune balance in the tumor into an immune-suppressive microenvironment. High neutrophil counts, in particular if of an immature nature, are associated with poor prognosis in cancer patients. Similarly, high monocyte counts are also associated with poor cancer prognosis.

BeyondSpring derived the data from the Phase 2 portion of Study 105, which evaluated Plinabulin’s potential to prevent CIN in patients with non-small cell lung cancer (NSCLC) following docetaxel chemotherapy. BeyondSpring evaluated the immune profile of Neulasta and Plinabulin, by analyzing the immune markers NLR (Neutrophil-to-Lymphocyte Ratio) and LMR (Lymphocyte-to-Monocyte Ratio), as well as the appearance of immature neutrophils (such as promyelocytes, myelocytes and bands) in the peripheral blood of NSCLC patients, who were treated with either Plinabulin at 20 mg/m2 (n=14) or Neulasta at 6 mg (n=14). NLR values of >5 and LMR values of <3.2, as well as immature neutrophils, are associated with immune suppression and poor cancer prognosis.

The data demonstrated that, in contrast to Neulasta, Plinabulin did not show NLR>5 or LMR <3.2 values. Promyelocytes or myelocytes were observed in 77% of patients given Neulasta, compared to 14% of patients given Plinabulin (p<0.001), and neutrophil bands were observed in more than 25% of patients given Neulasta, compared to 0% of patients given Plinabulin (p<0.03).

“While both Plinabulin and Neulasta monotherapy demonstrated equal effects in the prevention of CIN in terms of how often and how long patients experienced severe neutropenia in Study 105, this added demonstration of a potentially superior immune profile over Neulasta has distinct advantages. We now recognize the importance of our immune system in fighting cancer, and the avoidance of suppression of our immune system has the potential to result in better cancer outcomes and prognosis. A leading trend is to combine immunotherapy with chemotherapy, and the latter is known to induce CIN. With immune/chemotherapy combination, Plinabulin has the potential to offer advantages over Neulasta and G-CSFs in general for the prevention of CIN, to enable the best possible immune therapeutic efficacy,” said Dr. Ramon Mohanlal, EVP and Chief Medical Officer at BeyondSpring.

“Not only does Plinabulin appear to have immune-enhancing anticancer potential, but there is growing evidence supporting a superior product profile for the prevention of CIN. We previously reported a bone pain benefit with Plinabulin over Neulasta. Plinabulin prevents not only chemotherapy-induced neutropenia, but also chemotherapy-induced thrombocytopenia. This new observation of avoidance of an immune suppressive potential as was observed with Neulasta adds to the list of differentiating features observed in clinical trials to-date for Plinabulin and sets the stage for Plinabulin as a novel CIN treatment with potential for a superior product profile,” added Dr. Lan Huang, BeyondSpring’s CEO and Co-founder.

About Study 105
The study evaluated patients with advanced or metastatic NSCLC after failing platinum-based therapy and was designed as a multicenter, open label, randomized study. In a head-to-head comparison of Plinabulin with Neulasta, a long-acting G-CSF, in a total of 55 patients, Plinabulin was shown to be comparable to Neulasta for the prevention of CIN, as assessed by the occurrence of severe (grade 4) neutropenia and duration of severe neutropenia (DSN) in the first cycle.

Plinabulin was given as a single dose per cycle 30 minutes after docetaxel chemotherapy, while Neulasta was given 24 hours after docetaxel chemotherapy, consistent with its approved product label. The Phase 2 portion met its primary endpoint, which was to determine the recommended Phase 3 Plinabulin dose, and the Phase 3 trial is ongoing.

About Plinabulin 
Plinabulin, a marine-derived small-molecule, is BeyondSpring’s lead asset and is currently in late-stage clinical development for the prevention of chemo-induced neutropenia and as an anticancer therapy in non-small cell lung cancer. Studies of Plinabulin's mechanism of action indicate that Plinabulin activates GEF-H1, a guanine nucleotide exchange factor. GEF-H1 activates downstream transduction pathways leading to the maturation of dendritic cells, which in turn leads to T-cell activation and the up-regulate of IL6 in the tissue micro environment, contributing to the prevention of neutropenia.

About Chemotherapy-Induced Neutropenia
Chemotherapy-induced neutropenia is a common side effect in cancer patients undergoing treatment that involves the destruction of a type of white blood cell, the neutrophil, which is a patient’s first line of defense against infections. Patients with grade 4 (severe) neutropenia have an abnormally low concentration of neutrophils, making these patients more susceptible to bacterial and fungal infections and sepsis, which can require hospitalization.

The current standard of care for chemotherapy-induced neutropenia prevention is G-CSF monotherapy. However, G-CSF monotherapy has limitations as described in its product information summary. As many as 90 percent of patients on chemotherapy and G-CSF monotherapy may still experience grade 3/4 neutropenia. NCCN guidelines require that patients with grade 3/4 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.

About BeyondSpring
BeyondSpring is a global, clinical-stage biopharmaceutical company developing innovative immuno-oncology cancer therapies with a robust pipeline from internal development and from collaboration with the University of Washington in de novo drug discovery using a ubiquitination platform. 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 a seasoned management team with many years of experience bringing drugs to the global market.

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," "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.

Neulasta is a registered trademark of Amgen, Inc.

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Argot Partners

BeyondSpring, Inc.