Press Release

New Data Shows Addition of BeyondSpring’s Plinabulin Reverses Neulasta’s Potential Immune-Suppressive Phenotype in Treating Chemotherapy-Induced Neutropenia

BeyondSpring to Present Results at 2019 ASCO-SITC Clinical Immuno-Oncology Symposium 

NEW YORK, Feb. 26, 2019 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced new clinical results from its Study 106 program for lead asset Plinabulin, which demonstrates that combining Plinabulin with Neulasta (pegfilgrastim) not only improves overall efficacy for chemotherapy-induced neutropenia (CIN) treatment but also reverses Neulasta’s potential immune-suppressive phenotype. 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, “A Phase II trial with the Combination of Plinabulin and Pegfilgrastim: Evaluation of the Reversal of Peg’s Immune-Suppressive Potential by the Addition of Plin to Peg,” at the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium. BeyondSpring’s presentation will take place on March 1 at 11:30 a.m. to 1 p.m. and 5:30 to 6:30 p.m. local time as part of Poster Session B. 

Neulasta, a long-acting G-CSF and the current standard of care for CIN, is believed to activate the bone marrow, resulting in an overproduction of neutrophils, many of which are immature. Immature neutrophils can make their way to the tumor tissue and make the microenvironment immune-suppressive. Established markers for immune-suppression are high Neutrophil-to Lymphocyte Ratio (NLR>5) and low Monocyte-to-Lymphocyte Ratio (MLR<3.2), which are associated with low survival outcomes in cancer patients. Previously, BeyondSpring presented data from its Study 105 (using docetaxel as an example intermediate-risk chemotherapy), which showed that Neulasta, but not Plinabulin, caused levels of NLR>5 and MLR<3.2 in most patients (Blayney, ESMO 2018, SITC 2018). 

In its Study 106 (using TAC, or Taxotere, Doxorubicin and Cyclophosphamide, as an example of high-risk chemotherapy), BeyondSpring evaluated whether combining Plinabulin with Neulasta would reverse the immune-suppressive neutrophil profile induced by Neulasta. Breast cancer patients received TAC chemotherapy, followed by Neulasta monotherapy (6 mg; n=22), Plinabulin monotherapy (20 mg/m2; n=15) or Plinabulin combined with Neulasta (n=21) and analyzed NLR levels.  

The Plinabulin and Neulasta combination data shows better efficacy for the treatment of CIN, versus Neulasta alone, while preventing neutrophil overproduction. The percentage of patients with grade 4 neutropenia was lowered from 59 percent with Neulasta alone to 38 percent with the combination, and the percentage of patients with an absolute neutrophil count (ANC) exceeding the upper limit of what is considered normal was lowered from 50 percent with Neulasta alone to 31 percent with Neulasta and Plinabulin. Additionally, immune-suppressive NLR levels were lower (<25 percent of patients) in the Plinabulin / Neulasta combination, versus Neulasta alone (>50 percent of patients; p<0.0007 in the cycle). The MLR data showed a similar trend as well.  

“These new results from our poster presentation at this year’s ASCO-SITC Symposium, which marks BeyondSpring’s first abstract for Phase 2 of Study 106, provide additional rationale for developing Plinabulin in combination with Neulasta,” said Dr. Blayney. “This combination provides immense clinical benefit and reinforces earlier data from our studies with Plinabulin.”  

“The cancer treatment landscape is increasingly moving toward immunotherapy / chemotherapy combinations that also cause CIN,” added Dr. Ramon Mohanlal, EVP of R&D and Chief Medical Officer at BeyondSpring. “With high-risk febrile neutropenia, and with immunotherapy / chemotherapy combinations, the Plinabulin and Neulasta combination is expected to provide superior protection against CIN while avoiding a predominant immune-suppressive tumor microenvironment.”  

About Plinabulin
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 in non-small cell lung cancer. 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. 

About Chemotherapy-Induced Neutropenia
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. The current standard of care for CIN 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 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 and 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)). A reduction in dose of as little as 15 percent can reduce long-term survival by as much as 50 percent (Bonadonna, Med Oncol 29:1495–1501 (2012)).  

As many as 70 percent of patients using G-CSF monotherapy experience bone pain while on G-CSF monotherapy (Moore et al., Annals of Pharmacotherapy 51(9): 797-803 (2017)). Additionally, 25 percent of patients report that the pain is severe. 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 (Lalami et al., Critical Reviews in Oncology / Hematology 120: 163-179 (2017)). 

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 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. 

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.  

Contact:
Media Relations:
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KCSA Strategic Communications
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BeyondSpring, Inc.