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November 11, 2019

BeyondSpring's Single-Blinded Design (for Patients Only) of Phase 3 Study 103 (DUBLIN-3) Prevented Premature Patient Drop-Out: Data Accepted for Presentation at SITC 2019

Premature Patient Drop-Out Rate from Comparator Arm Might Contribute to Negative Trial Outcome, and was Avoided in DUBLIN-3

NEW YORK, Nov. 11, 2019 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies, today announced that the Company’s novel trial design for Study 103 with lead asset, Plinabulin, was selected for poster presentation at this year’s Society for Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, MD. The poster, titled, “Validation of a Single-Blinded (Patients Only) Study Design for the Prevention of Premature Patient Consent Withdrawal in the Immuno-Oncology Trial DUBLIN-3,” was presented on November 9.

As cancer patients generally prefer immunotherapy over chemotherapy, they may prematurely withdraw their consent to participate in a clinical trial if they are allocated to the chemotherapy comparator arm, which may negatively impact the study’s outcome. The PD-L1 inhibitor Avelumab in the open-label trial Javelin failed to meet its primary objective to demonstrate a survival benefit versus the standard of care Docetaxel comparator arm, in stage IIIB/IV NSCLC patients. One of the reasons for this negative trial outcome was the high percentage of premature drop-out rate from the Docetaxel arm (75 mg/m2), according to the Javelin study authors.

BeyondSpring’s single-blinded (for patients only) Phase 3 Study 103 (DUBLIN-3) evaluated overall survival with the immune-enhancing agent Plinabulin in combination with Docetaxel 75 mg/m2 versus Docetaxel 75 mg/m2 in stage IIIB/IV NSCLC patients. BeyondSpring analyzed data on patient drop-out rate obtained around the first interim analysis of DUBLIN-3 and compared the premature drop-out rates from DUBLIN-3 with that of the immunotherapy trial Javelin, both trials conducted in stage IIIB/IV NSCLC subjects and with Docetaxel 75 mg/m2 as comparator. However, DUBLIN-3 was single-blinded and the Javelin trial was open label (unblinded).

The data showed that the single-blinded design employed in DUBLIN-3 statistically significantly prevented premature patient drop-out from the Docetaxel arm compared to the study with Avelumab (Javelin): 8 percent versus 1 percent (premature drop-out rate for Javelin vs DUBLIN-3 (P=0.001).

"The results from this analysis validate the effectiveness of a single-blinded (for patients only) study design for the prevention of premature patient drop-out from the chemotherapy comparator arm. Since premature patient drop out in the comparator arm is associated with negative trial outcome results, these observations may prove favorable in obtaining a positive outcome in DUBLIN-3. This finding may also be relevant for the design of future IO trials,” said Dr. Ramon Mohanlal, BeyondSpring’s Executive Vice President, R&D, and Chief Medical Officer. “Following the first pre-planned interim analysis with Study 103 in the first quarter of 2019, the study continued without modifications. Our second interim analysis to evaluate overall survival is projected to be triggered late 2019.”

BeyondSpring’s global Phase 3 Study 103 trial evaluates EGFR wild-type patients (target n=554) stratified for region (Asia / non-Asia) who are receiving second- and third-line therapy with the Plinabulin/Docetaxel combination, or Docetaxel alone. Patients should have at least one measurable lung lesion located in the lung and must have failed a prior platinum-based regimen. In addition, patients who failed prior PD-1/PD-L1 immunotherapy could enter the study. The primary endpoint is overall survival.

In Phase 2 trials in NSCLC stage IIIB/IV patients with a measurable lung lesion in the lung, Plinabulin added to Docetaxel had a survival improvement of 4.6 months over Docetaxel alone (data presented at ASCO-SITC 2017) and also prevented Docetaxel-induced Neutropenia (data presented at ASH 2017, 2018), and improved QoL in NSCLC patients receiving Docetaxel (data presented at IASLC World Lung Conference 2019).

Since Docetaxel is the current standard of care in second- and third-line in stage IIIB/IV NSCLC, the addition of Plinabulin to Docetaxel has the potential to become the new standard of care in second- and third-line stage IIIB/IV NSCLC if the Phase 3 data confirms the Phase 2 data by showing superior efficacy, superior safety and superior QoL compared to Docetaxel monotherapy.

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 (NSCLC) and two Phase 3 clinical programs in the prevention of chemotherapy-induced neutropenia (CIN). BeyondSpring has strong R&D capabilities with a robust pipeline in addition to Plinabulin, including three immuno-oncology assets and a drug discovery platform using the ubiquitination degradation pathway. The Company also has a seasoned management team with many years of experience bringing drugs to the global market.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a marine-derived small molecule that sequesters tubulin heterodimers in a differentiated manner from other agents in this class. Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia (CIN). The anticancer benefits of 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. Plinabulin’s CIN data highlights the ability to boost the number of hematopoietic stem / progenitor cells (HSPCs), or lineage-/cKit+/Sca1+ (LSK) cells in mice. Effects on HSPCs could explain the ability of Plinabulin to not only treat CIN but also to reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients.

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.

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