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November 16, 2020

BeyondSpring Announces Positive Topline Results from its PROTECTIVE-2 Phase 3 Registrational Trial of Plinabulin in Combination with Pegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia

NEWYORK, November 16, 2020 (GLOBE NEWSWIRE) -- BeyondSpring (the “Company” or“BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused onthe development of innovative cancer therapies, today announced positivetopline data from its PROTECTIVE-2 Phase 3 registrational study showing that plinabulinin combination with pegfilgrastim met the primary endpoint with statisticallysignificant improvement in the rate of prevention of Grade 4 neutropenia in Cycle1 (31.5% vs 13.6%, p=0.0015), as well as achieving statistical significancein all key secondary endpoints, including duration of severe neutropenia (DSN)and absolute neutrophil count (ANC) nadir.


The PROTECTIVE-2 Phase 3 study is a double-blind, active-controlled,global study that enrolled a total of 221 patients. Patients in the trial were treatedwith docetaxel, doxorubicin and cyclophosphamide (TAC, Day 1 dose) in a 21-daycycle with plinabulin (40 mg, Day 1 dose) + pegfilgrastim (6 mg, Day 2 dose)versus a single dose of pegfilgrastim (6 mg, Day 2 dose). The primary efficacyendpoint was rate of prevention of Grade 4 neutropenia.


Plinabulin in combination with pegfilgrastim showed astatistically significant improvement compared to pegfilgrastim alone, withtopline data summarized below. Data from all 221 patients were analyzed(combination arm n=111, pegfilgrastim arm n=110).

·        Primary endpoint (Rate of prevention of Grade4 neutropenia): 31.5% combo therapy vs. 13.6% pegfilgrastim monotherapy, 95% CI17.90 (7.13, 28.66),p= 0.0015

·        Key secondary endpoints:

o  DSN Cycle 1 Day 1-8 (ANC < 0.5 x 109 cells/L): p = 0.0065,

o  DSN Cycle 1: p = 0.03

o  Mean ANC nadir Cycle 1 (x 109 cells/L): p = 0.0002

o  Duration of profound neutropenia Cycle 1 (ANC< 0.1 x 109 cells/L): p = 0.0004,

According to literature, profoundneutropenia leads to 80% patient death in first week of infection1,and 48% febrile neutropenia, or FN, and 50% infection2.

·        Safety data:

o  Lower Grade 4 adverse event (AE) frequency (58.6%)for combination compared to 80.0% in pegfilgrastim monotherapy


“These data clearly demonstrate the potential for thiscombination to offer superior therapy compared to standard of care in the preventionof CIN,” said Douglas W. Blayney, M.D., Professor of Medicine at the StanfordUniversity School of Medicine and the global principal investigator for plinabulin'sCIN studies. “With current therapy, Grade 4 neutropenia still occurs inmore than 80% of patients after chemotherapy, primarily in Week 1 after chemotherapy,which increases Emergency Room visits and hospitalizations due to infection andfebrile neutropenia. Grade 4 neutropenia is also associated with increased mortalityand reduced long-term survival due to reduction, delay, or interruption ofchemotherapy. I would like to thank theparticipating patients, their families and the BeyondSpring team for theirdedicated work to advance this combination therapy for the prevention of CIN inchemotherapy patients.”


Ramon Mohanlal, M.D., Ph.D., Chief Medical Officer and ExecutiveVice President of Research and Development at BeyondSpring noted, “We arepleased to have received Breakthrough Therapy designation from both the U.S.FDA and China NMPA for the plinabulin combination in CIN, underscoring the unmetmedical need and potential benefit of the combination. We are working withregulatory agencies on the NDA submission, which is expected in Q1 2021 andhave also begun preparation for commercialization. In addition to Plinabulin beingdeveloped as a treatment option for the prevention of CIN, it is also beinginvestigated as a direct anticancer agent in a global Phase 3 trial of plinabulin+ docetaxel for non-small cell lung cancer (NSCLC), with final data read-out in 1H 2021.”


Conference Call and Webcast Information
BeyondSpring’s management will host a conference call and webcast today at 8:30a.m. Eastern Time. The dial-in numbers for the conference call are 1-877-451-6152(U.S.) or 1-201-389-0879 (international). Please reference conference ID: 13713406.A live webcast will be available on BeyondSpring’s website at www.beyondspringpharma.com under “Events& Presentations” in the Investors section. An archived replay of thewebcast will be available for 30 days.


1 Bodey et al. Ann Intern Med 64(2): 328(1966); 2 Bodey et al. Cancer 41(4): 1610 (1978)


About Plinabulin in PROTECTIVE-2 (Study 106) CINStudy
The Phase 3 portion of PROTECTIVE-2 is a double-blind and active controlledglobal study. It was designed to evaluate the safety and efficacy in breastcancer, treated with docetaxel, doxorubicin and cyclophosphamide (TAC, Day 1dose) in a 21-day cycle with plinabulin (40 mg, Day 1 dose) + Pegfilgrastim (6 mg,Day 2 dose) versus a single dose of Pegfilgrastim (6 mg, Day 2 dose).  TAC is an example of high febrile neutropenia riskchemotherapy; all G-CSF biosimilar studies use TAC in the pivotal studies.


Plinabulin and G-CSFs such as Pegfilgrastim are believed to havecomplementary mechanisms in preventing chemotherapy-induced neutropenia (CIN).This is a superiority study in CIN efficacy in the rate of prevention of Grade4 neutropenia, comparing the combination head-to-head against Pegfilgrastimalone. Literature shows that the Grade 4 neutropenia rate for TAC and Pegfilgrastimat 6 mg is 83 to 93 percent, which presents severe unmet medical needs.


The absolute neutrophil count (ANC) data, which are used tocalculate these endpoints, were obtained through central laboratory assessmentsby Covance Bioanalytical Methods using standardized and validated analyticaltests. Covance was the clinical contract research organization (CRO) forpatient recruitment and monitoring of global sites for this study.

About Chemotherapy Induced Neutropenia (CIN)

Patients receiving chemotherapy typically develop CIN, a severeside effect that increases the risk of infection with fever (also called febrileneutropenia, or “FN”), which necessitates ER/hospital visits. The updatedNational Comprehensive Cancer Network (NCCN) guidelines expanded the use of prophylacticG-CSFs, such as Pegfilgrastim, from only high risk patients (chemo FN rate>20%) to intermediate risk patients (FN rate between 10-20%) to avoidhospital/ER visits during the COVID-19 pandemic.  The revision of the NCCN guidelineseffectively increases the addressable market of patients who may benefit fromtreatment with plinabulin, if approved, to approximately 440,000 cancerpatients in the U.S. annually.  Plinabulinis designed to provide protection against the occurrence of CIN and its clinicalconsequences in week 1, or early onset action after chemotherapy.


About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is an investigational differentiatedimmune and stem cell modulator. Plinabulin is currently in late-stage clinicaldevelopment to increase overall survival in cancer patients, as well as toalleviate CIN.  Plinabulin had received BreakthroughTherapy Designation from China NMPA in CIN. The U.S. FDA granted Breakthrough Therapy designation to plinabulin forconcurrent administration with myelosuppressive chemotherapeutic regimens inpatients with non-myeloid malignancies for the prevention ofchemotherapy-induced neutropenia (CIN). The durable anticancer benefits of plinabulinobserved to date have been associated with its effect as a potentantigen-presenting cell (APC) inducer (through dendritic cell maturation) andT-cell activation (Chem and Cell Reports, 2019). Plinabulin’s CIN data highlightthe ability to boost the number of hematopoietic stem / progenitor cells(HSPCs), or lineage-/cKit+/Sca1+ (LSK) cells in mice. Effects on HSPCs couldexplain the potential ability of plinabulin to not only treat CIN with a rapidonset, but also to reduce chemotherapy-induced thrombocytopenia and increasecirculating CD34+ cells in patients.


Plinabulin currently is in an Expanded Access Program in theU.S.


About BeyondSpring
BeyondSpring is a global, clinical-stage biopharmaceutical company focused onthe development of innovative cancer therapies. BeyondSpring’s lead asset,  plinabulin, a first-in-class agent as animmune and stem cell modulator, is in a Phase 3 global clinical trial as adirect anticancer agent in the treatment of non-small cell lung cancer (NSCLC)and Phase 3 clinical programs in the prevention of CIN.  BeyondSpring has strong R&D capabilitieswith a robust pipeline in addition to plinabulin, including threeimmuno-oncology assets and a drug discovery platform using the proteindegradation pathway, which is being developed in a subsidiary company, SeedTherapeutics, Inc. The Company also has a seasoned management team with manyyears of experience bringing drugs to the global market. BeyondSpring isheadquartered in New York City.

Cautionary Note Regarding Forward-Looking Statements
This press release includes forward-looking statements that are not historicalfacts. Words such as "will," "expect,""anticipate," "plan," "believe,""design," "may," "future," "estimate,""predict," "objective," "goal," or variationsthereof and variations of such words and similar expressions are intended toidentify such forward-looking statements. Forward-looking statements are basedon BeyondSpring's current knowledge and its present beliefs and expectationsregarding possible future events and are subject to risks, uncertainties andassumptions. Actual results and the timing of events could differ materially fromthose anticipated in these forward-looking statements as a result of severalfactors including, but not limited to, difficulties raising the anticipatedamount needed to finance the Company's future operations on terms acceptable tothe Company, if at all, unexpected results of clinical trials, delays or denialin regulatory approval process, results that do not meet our expectationsregarding the potential safety, the ultimate efficacy or clinical utility ofour product candidates, increased competition in the market, and other risksdescribed in BeyondSpring’s most recent Form 20-F on file with the U.S.Securities and Exchange Commission. All forward-looking statements made hereinspeak only as of the date of this release and BeyondSpring undertakes no obligationto update publicly such forward-looking statements to reflect subsequent eventsor circumstances, except as otherwise required by law.

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