– Data from U.S. Phase 1 dose escalation investigator-initiated trial demonstrated favorable safety and tolerability.

– Plinabulin, in combination with nivolumab and ipilimumab, shows 46% objective response rate (ORR) in 13 evaluable patients with PD-1/PD-L1 naïve or resistant tumors in 2nd line and beyond in small cell lung cancer (SCLC).

– Plinabulin combination was able to re-sensitize tumors that had progressed on prior PD-1/PD-L1 inhibitors with 43% ORR (3 partial responses with tumor reduction >50%).

NEW YORK, May 24, 2021 (GLOBE NEWSWIRE) — BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced a poster presentation of an investigator-initiated Phase 1 study at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 4 – 8, 2021. The company’s lead asset plinabulin, a selective immunomodulating microtubule-binding agent (SIMBA), was combined with nivolumab and ipilimumab in the treatment of 2nd and 3rd line small cell lung cancer (SCLC) in a Phase 1 study of 16 patients from 6 U.S. clinical centers. There is a severe unmet medical need in 2nd and 3rd line small cell lung cancer (SCLC) patients, as immune therapies (PD-1/PD-L1 inhibitors or PD-1+CTLA-4 inhibitors) have only demonstrated a 10-23% objective response rate (ORR) and limited median progression free survival (PFS) at 1.4 to 2.6 months (Iams et al. 2020).

The poster, titled “A Phase I Trial of Plinabulin in Combination with Nivolumab and Ipilimumab in Patients with Recurrent Small Cell Lung Cancer (SCLC),” will be presented at 9 a.m. ET on June 4, 2021 at Lung Cancer Poster Session (Abstract #8570). The poster describes an investigator-initiated clinical trial, led by Jyoti Malhotra, MD, MPH, Robert Wood Johnson Medical School, Rutgers University, and conducted within the Big Ten Cancer Research Consortium. It highlights preliminary data demonstrating synergistic anti-cancer effects of the combination of plinabulin, nivolumab and ipilimumab, with an overall 46% ORR in 13 evaluable patients with PD-1/PD-L1 naïve or resistant tumors in 2nd and 3rd line SCLC.

In the Phase 1 dose escalation study evaluating 20 mg/m2 and 30 mg/m2 doses of plinabulin combined with nivolumab and ipilimumab in 16 patients, the 30 mg/m2 dose was selected for the Phase 2 trial. All 16 patients were evaluated for safety, and 13 patients were evaluated for efficacy.

  • The combination demonstrated favorable safety and tolerability. There were no Grade 4 events in the 16 patients studied, and only 12.5% experienced Grade 3/4 IR-AEs, compared to 37% reported with nivolumab + ipilimumab in SCLC.
  • ORR was 50% for the six patients receiving the triple IO combination as second line therapy after platinum. Three patients had partial responses (PR), with best tumor reduction at target lesions of 100%, 53% and 45%, respectively.
  • ORR was 43% for the seven patients receiving the triple IO combination as third line therapy, who had either failed or had not responded to platinum and PD-1/PD-L1 inhibitors. Three patients had PRs, with best tumor reductions at target lesions of 78%, 75% and 52%, respectively. Duration of therapy for these 3 PR patients was 18 months, five months (still on treatment) and three months, respectively.

“SCLC still represents an area of tremendous unmet medical need. This study supports the hypothesis that the addition of plinabulin to a nivolumab+ ipilimumab regimen could increase response rates in 2nd/3rd line SCLC. The study is small, but some patients who previously developed resistance to checkpoint inhibitors had durable responses and large tumor reduction. The study also looked at immune-related AEs and it is very exciting to see support for our hypothesis that plinabulin, due to PDE-4 inhibition, could reduce these treatment-limiting AEs, along with increased efficacy in tumor response rates,” said Dr. Malhotra.

Ramon Mohanlal M.D., Ph.D., Chief Medical Officer and Executive Vice President of Research and Development at BeyondSpring added, “Plinabulin is a potent agent to mature and activate dendritic cells, the most important antigen-presenting cells. By adding plinabulin to nivolumab + ipilimumab, we enhance both antigen generation and antigen presentation to the T-cell repertoire. This is a proof-of-concept study, and positions plinabulin to be studied as a potential ‘cornerstone’ agent by adding to existing and emerging IO regimens to increase response rates, reverse tolerance, lower immune-related AEs and expand eligible patient populations.”

For more information of this trial (NCT03575793), please visit clinicaltrials.gov.

Iams, W.T., Porter, J., Horn, L. Immunotherapeutic approaches for small cell lung cancer, Nat Rev Clin Oncol, 2020 May;17(5):300-312.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), an NDA ready asset for CIN prevention indication and a phase 3 anti-cancer candidate for 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 PD1/PD-L1 antibodies.

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 non-small cell lung cancer (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. 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.

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 the 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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