BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing, and with Priority Review, the Company’s New Drug Application (NDA) seeking approval for use of plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN). Plinabulin, a novel, intravenous infused small molecule, acts as a selective immunomodulating microtubule-binding agent (SIMBA), with immune anti-cancer activities, and broad activities in prevention of CIN across chemotherapy and cancer types.

Priority Review is granted by the FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions when compared to standard of care. In general, the FDA’s Priority Review designation accelerates the review time from 10 months to a goal of six months from the date of acceptance of the filing. The FDA has a Prescription Drug User Fee Act (PDUFA) target action date set for the plinabulin NDA of November 30, 2021.

The U.S. FDA and China NMPA previously granted Breakthrough Therapy Designation in September 2020 for plinabulin and G-CSF combination for “concurrent administration with myelosuppressive chemotherapeutic regimens in patients with non-myeloid malignancies for the prevention of CIN.”

“We are pleased that the FDA has accepted with priority review our NDA filing for plinabulin, which is one of the key milestones for this product in 2021. We look forward to continue to work closely with the FDA through the review process,” said Dr. Lan Huang, co-founder, CEO and chairwoman of BeyondSpring. “Chemotherapy is a very important therapy regimen for cancer patients, even more so with its approval in combination with checkpoint inhibitors. With COVID-19, the NCCN panel had updated the guidelines to potentially double the patient population included in CIN prevention. If approved, plinabulin and G-CSF combination would be an important new and improved option to prevent CIN for approximately 467,500 cancer patients in the U.S. annually.”

This NDA submission included pivotal study PROTECTIVE-2 Phase 3 data in addition to five supportive trials of over 1200 patients. PROTECTIVE-2 Phase 3 registration study is a randomized, double-blind, controlled global trial, which showed that plinabulin in combination with pegfilgrastim demonstrated superior CIN prevention benefit, compared to pegfilgrastim alone. The study met the primary endpoint, in the rate of prevention of grade 4 neutropenia in Cycle 1 (improved from 13.6% to 31.5%, p=0.0015) and met all key secondary endpoints, including duration of severe neutropenia (DSN) and absolute neutrophil count (ANC) nadir. In addition, the combination reduced clinical complications such as incidence and severity of febrile neutropenia (FN) and incidence and duration of hospitalization for FN patients. The combination is well tolerated, with an over 20% reduction of Grade 4 Treatment-Emergent Adverse Events (TEAEs), including bone pain reduction, and importantly, a Quality of Life (QoL) benefit compared to pegfilgrastim alone.

About CIN

CIN remains a severely unmet medical need and is the primary cause for the 4D’s (Decrease, Delay, Discontinue dose and Downgrade regimen) that compromise carefully selected cancer treatment regimens. Treatment or prevention of CIN with G-CSF has been the standard of care since Neupogen? was approved in 1991. The main benefit of G-CSF treatment, however, is in Week 2 after chemotherapy. Week 1 after chemotherapy is considered the “neutropenia vulnerability gap” where over 75% of CIN-related clinical complications occur, including febrile neutropenia, infection, hospitalization and death. Plinabulin is the first drug seeking FDA approval that has the potential to fill this gap. Combining plinabulin and G-CSF may maximize the protection of patients for the full cycle of chemotherapy, as demonstrated in the PROTECTIVE-2 Phase 3 registration study.

Each year in the U.S., 110,000 patients receiving chemotherapy are hospitalized after developing CIN, a severe side effect that increases the risk of infection with fever (also called FN). Due to the COVID-19 pandemic, the updated National Comprehensive Cancer Network (NCCN) guidelines expanded the use of prophylactic G-CSFs, including pegfilgrastim, from high-risk patients only (chemo FN rate >20%), to include intermediate-risk patients (FN rate between 10-20%), to reduce the number of hospital/ER visits related to CIN. The revision of the NCCN guidelines effectively increases the addressable market of patients to approximately 467,500 cancer patients in the U.S. annually.

About Plinabulin

Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA). It is a novel, intravenous infused, patent-protected, NDA ready asset for CIN prevention indication and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC). Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received breakthrough designation from both US and China FDA for CIN prevention indication. As a “pipeline in a drug,” plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody resistant patients.

About BeyondSpring

Headquartered in New York City, BeyondSpring is a global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have high unmet medical needs. BeyondSpring’s first-in-class lead asset plinabulin, is being developed as a “pipeline in a drug.” It is filed for approval in the US and China for the prevention of chemotherapy-induced neutropenia (CIN) and has a fully enrolled pivotal study to test an anti-cancer benefit with an overall survival primary endpoint in NSCLC. Additionally, it is being broadly studied in combination with various immuno-oncology regimens that could boost the effects of PD-1 / PD-L1 antibodies, and re-sensitize PD-1/PD-L1 antibody resistant patients.
In addition to plinabulin, BeyondSpring’s extensive pipeline includes three pre-clinical immuno-oncology assets and a subsidiary, SEED Therapeutics, which is leveraging a proprietary targeted protein degradation drug discovery platform.