BeyondSpring Announces Data & Safety Monitoring Board Recommendation for Plinabulin to Continue NSCLC Phase 3 Dublin-3 Study Without Modification

June 03, 2020

– DSMB Reviewed Over 500 Patients’ Data in Second Interim Analysis to Assess Overall Benefit / Risk with Plinabulin in Second- and Third-Line, EGFR Wild-Type NSCLC –
NEW YORK, June 03, 2020 (GLOBE NEWSWIRE) — BeyondSpring (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies, today announced that the Company has reached the second interim analysis for its Phase 3 Dublin-3 (Study 103) in the treatment of non-small cell lung cancer (NSCLC) with lead asset, Plinabulin. Upon reviewing the safety and efficacy data of over 500 patients and approximately 300 pre-specified death events, the Data & Safety Monitoring Board (DSMB) has advised BeyondSpring to continue the study without any modifications. Study 103 evaluates the anti-cancer effects of Plinabulin in combination with docetaxel, compared to docetaxel alone, in second- / third-line Epidermal Growth Factor Receptor (EGFR) wild-type NSCLC patients, with a primary endpoint of overall survival (OS).
EGFR wild-type NSCLC patients make up 85 percent of the NSCLC population; second- / third- line NSCLC with EGFR wild-type represents one of the most significant clinical challenges with limited treatment options. Currently approved I/O therapies and the chemotherapy pemetrexed have advanced to first-line treatment, leaving a therapeutic void for patients whose cancer progresses. The remaining approved two chemotherapy options, docetaxel and the docetaxel-ramucirumab combination, have significant limitations. These limitations force second- / third-line patients to choose between minimal gains in OS (less than 1.5 months for docetaxel-ramucirumab) over docetaxel alone with extremely high severe (Grades 3 and 4) neutropenia rates at over 40 percent with both options.
The onslaught of COVID-19 is causing oncologists to reconsider the impact of neutropenia on cancer care. Recent studies indicate that the death rate for NSCLC patients afflicted with COVID-19 are as high as 55 percent1 in the New York healthcare system, making the avoidance of neutropenia, as well as OS extension, the key priorities in cancer care.
In a Phase 2 clinical trial, the Plinabulin-docetaxel combination demonstrated the efficacy benefit of a long duration of response (12.7 months) and a median OS benefit of 4.6 months (retrospective analysis in the measurable lung lesion subset) over docetaxel, the standard of care, alone. Most importantly, in that study, adding Plinabulin to docetaxel reduced the frequency of patients who experienced Grade 4 neutropenia from 33.8 percent to less than 5 percent (p<0.0003). Thus, the Plinabulin-docetaxel combination potentially improves on anti-cancer efficacy, while reducing toxicity, compared with docetaxel alone.
“The Dublin-3 study was designed to quantify the immune-enhancing potential of Plinabulin,” said Dr. Ramon Mohanlal, BeyondSpring’s Chief Medical Officer and Executive Vice President, Research and Development. “We selected tumors with a measurable lung lesion (per RECIST 1.1),which has more TMB (tumor mutation burden) to prospectively test this population (which had encouraging results in our Phase 2 analysis). This population – over 70 percent of EGFR wild-type NSCLC patients – represents new subclones with a higher probability of harboring antigens capable of stimulating the immune system (Mohanlal, ESMO 2019; Mohanlal, IASLC / World Conference on Lung Cancer, 2019). The DSMB’s green light is an encouraging step as we continue this trial without modifications following our second interim dataset review.”
“As a result of the current COVID-19 pandemic, lung cancer patients who are infected by the virus have a 55 percent death rate1. This population is already facing tremendously high odds, and the pandemic provides another proof point as to the need for additional treatment options,” added Dr. Lan Huang, BeyondSpring’s CEO and co-founder. “The Plinabulin-docetaxel combination may offer a favorable benefit / risk profile in the potential for extending patient survival and reducing severe neutropenia associated with docetaxel.”
1. Mehta V et al., Cancer Discovery May 1, 2020 online; DOI: 10.1158/2159-8290.CD-20-0516.

About BeyondSpring
BeyondSpring is a global, clinical-stage biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies. BeyondSpring’s lead asset, first-in-class agent Plinabulin as an immune and stem cell modulator, 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. BeyondSpring is headquartered in New York City.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a differentiated immune and stem cell modulator. 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 durable anticancer benefits of Plinabulin have been associated with its effect as a potent antigen-presenting cell (APC) inducer (through dendritic cell maturation) and T-cell activation (Chem and Cell Reports, 2019). 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 with a rapid onset, but also to reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients.

About Dublin-3 NSCLC Phase 3 (Study 103)
Dublin-3 NSCLC is a global Phase 3 randomized, controlled clinical trial comparing the combination of Plinabulin and docetaxel to an active control arm of docetaxel alone (1:1 randomization) in second- and third-line NSCLC patients who failed their first-line of platinum doublet therapies, and who are Epidermal Growth Factor Receptor (EGFR) wild-type. Docetaxel is given on Day 1 in both arms at 75 mg/m2 in each 21-day cycle. Plinabulin is given on Day 1, one hour after docetaxel, and on Day 8, both at 30 mg/m2 in each cycle. Over 500 patients had been enrolled to date.
Important inclusion criteria include patients with measurable lung lesions (RECIST 1.1 definition) using central lab evaluation. The study stratifies PD-1 / PD-L1 antibody-failed patients versus PD-1 / PD-L1 antibody-naïve patients. The primary endpoint for the study is overall survival, and secondary endpoints are Progression Free Survival (PFS), Overall Response Rate (ORR), Duration of Response (DOR), Grade 4 neutropenia and Quality of Life.

About Current Standard of Care for Second- / Third-Line, EGFR Wild-Type NSCLC Patients
There are only four therapies approved in this population, with a median survival of around eight to 12 months. These four therapies include docetaxel, pemetrexed, the ramucirumab-docetaxel combination and PD-1 / PD-L1 monotherapy. With PD-1 antibodies and pemetrexed moving into first-line NSCLC treatment, the current standard care for second- / third-line patients in the U.S. is either docetaxel or the ramucirumab-docetaxel combination, with a limited median OS of eight to 10 months and a high severe neutropenia rate of 40 percent and 49 percent, respectively.
Tyrosine Kinase Inhibitors (TKIs), including Tarceva, are effective for EGFR-mutant, second- / third-line NSCLC patients, with median OS of 18.3 months. However, for EGFR wild-type patients, docetaxel is better than Tarceva, one type of TKI, in median OS (5.4 months for Tarceva versus 8.2 months for docetaxel, p=0.05) in the TAILOR study2.
2. Garassino MC et al. Lancet Oncol. 2013 Sep;14(10):981-8

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.