Press Release

BeyondSpring’s Lead Asset, Plinabulin, Prevents Docetaxel Chemo-Induced-Neutropenia (CIN) Due to a Mechanism of Action Differentiated from G-CSF

Evidence of Neutrophil Demargination and Bone Marrow Transit Time Reduction by Plinabulin Presented at Joint Meeting of the Society for Leukocyte Biology and International Endotoxin and Innate Immunity Society

NEW YORK, Oct. 16, 2018 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ:BYSI), a global, clinical-stage biopharmaceutical company focused on the development of innovative cancer therapies, will present clinical trial data on its lead asset, Plinabulin, during a presentation at the 2018 Joint Meeting of the Society for Leukocyte Biology and International Endotoxin and Innate Immunity Society in Chandler, Ariz. The presentation is titled, “Plinabulin-Associated Neutrophil Demargination: Evidence for a Clinically Relevant Mechanism of Action for the Prevention of Chemotherapy-Induced-Neutropenia.”

Non-small cell lung cancer (NSCLC) patients received docetaxel chemotherapy plus Plinabulin (in doses up to 20 mg/m2) versus docetaxel alone in BeyondSpring’s Phase 2 Study 105. The beneficial effect of Plinabulin on docetaxel-induced CIN was measured at doses of 0 (n=14), 5 (n=14), 10 (n=13) or 20 (n=14) mg/m2 in NSCLC patients. A nonlinear mixed effects pharmacokinetic/pharmacodynamic (PK/PD) modeling approach was used to analyze absolute neutrophil count (ANC) to determine turnover rate (production and clearance) of ANC with Plinabulin (at different doses) and without Plinabulin.

  • Evidence of Clinically Relevant Neutrophil Demargination: In the control arm without Plinabulin, the increase in mean absolute neutrophil count (ANC) on Day 2 versus Day 1 was minimal (at 0.1x10E9/L) and not statistically significant (p=0.5). In the Plinabulin arms, on Day 2 versus Day 1, ANC increased due to demargination by 1.8, 1.5 and 3.3x10E9/L at Plinabulin doses of 5 (p<0.02), 10 (p=0.09) and 20 (p<0.004) mg/ m2, respectively. Overall, the ANC demargination effects of Plinabulin on Day 2 were statistically significant (p=0.038) and clinically relevant as it correlated with ANC protection at nadir of the cycle (p<0.05).
     
  • Evidence of Bone Marrow Transit Time Reduction: Plinabulin significantly shortened ANC steady state Synthesis Time (p<0.0068), which is indicative of the accelerated release of neutrophils from the bone marrow.

The observed effects of Plinabulin on ANC demargination and bone marrow transit time reduction are consistent with IL-6 signaling in bone marrow and tissue microenvironment1, a unique mechanism of action and a potential complementary therapeutic effect in working with G-CSF.

“We previously presented data showing Plinabulin’s superior product profile, with more limited bone pain and protection against thrombocytopenia, for prevention of docetaxel CIN with its different mechanism of action from pegfilgrastim. We now show additional clinically relevant findings – increased ANC demargination and reduced ANC transit time consistent with Plinabulin’s IL-6 signaling – further differentiating Plinabulin’s MoA from pegfilgrastim,” said Dr. Douglas Blayney, global Principal Investigator for BeyondSpring’s CIN development program and Professor of Medicine at Stanford University Medical Center.

“Plinabulin’s MoA in CIN is highly differentiated from G-CSF, which makes Plinabulin potentially complimentary to Neulasta for the prevention of CIN. Furthermore, there is a potential for increasing efficacy, while reducing safety concerns by combining these two classes of CIN agents. This provides a strong rationale for a development strategy in CIN that combines these two agents to create a treatment that is superior to each of them alone, both in terms of efficacy and safety/tolerability,” added Dr. Ramon Mohanlal, EVP and Chief Medical Officer at BeyondSpring.

1 Suwa et al, Am J Physiol 2000;279:H2954-H2960

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 pegfilgrastim (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 currently in late-stage clinical development for the prevention of CIN and as an anticancer therapy in NSCLC. 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, leading to T-cell activation and the up-regulate of IL6 in tissue micro environment, which contributes to the prevention of neutropenia.

About Chemotherapy-Induced Neutropenia (CIN)
CIN 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 / sepsis, which can require hospitalization.

The current standard of care for CIN prevention is G-CSF. However, G-CSF has limitations as described in its product information summary. Neutropenia, if severe enough, may cause doctors to lower target doses of chemotherapy, end therapy early and / or delay chemotherapy cycles, each of which has a negative effect on 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 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 (NSCLC) and two Phase 2/3 clinical programs in the prevention of chemotherapy-induced neutropenia (CIN). 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.

Contact:
Media Relations:
Caitlin Kasunich / Amrita Singh
KCSA Strategic Communications
212.896.1241 / 212.896.1207
ckasunich@kcsa.com / asingh@kcsa.com

Investor Relations:
Laura Perry / Joe Rayne
Argot Partners
212.600.1902
BeyondSpring@argotpartners.com

BeyondSpring, Inc.