BeyondSpring Announces First Patient Dosed in a Triple Combination Study with Plinabulin, PD-1/PD-L1 Inhibitor and Radiotherapy for the Reversal of Resistance to PD-1/PD-L1 Inhibitors in Patients with Advanced Solid Tumors

• Resistance to immunotherapy is a severe unmet medical need that plinabulin aims to address in combination with checkpoint inhibitors and radiotherapy
• First patient who failed Keytruda and chemotherapy has been dosed with plinabulin, Keytruda and radiation combination in non-small cell lung cancer (NSCLC)

NEW YORK, June 04, 2021 (GLOBE NEWSWIRE) — BeyondSpring (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced that the first patient had been dosed in the Phase 1b/2 investigator-initiated trial, studying the safety and tolerability of plinabulin, in triple combination therapy with both PD-1/PD-L1 antibody (mAb) and radiation therapy (RT). This triple combination is actively recruiting at The University of Texas MD Anderson Cancer Center, with Dr. Vivek Subbiah as principal investigator, in seven metastatic or locally advanced cancers, which include bladder cancer, melanoma, Merkel cell cancer, MSI-H cancers (of any histology), non-small cell lung cancer (NSCLC), renal cell cancer, and small cell lung cancer (SCLC).

The study is titled “An Open-label, Single-center, Phase 1b/2 Study to Evaluate the Safety of Plinabulin in Combination with Radiation/Immunotherapy in Patients with Select Advanced Malignancies after progression on PD-1 or PD-L1 Targeted Antibodies.”

• Patients will receive a triple combo treatment of RT + plinabulin + anti-PD-1/PD-L1 mAb in Cycle 1, followed by anti-PD-1/PD-L1 mAb and plinabulin combo regimen in Cycle 2 and beyond until disease progression or development of unacceptable toxicity, withdrawal from study treatment, or discontinuation of this study.
• Plinabulin will be tested in combination with five different PD-1/PD-L1 immunotherapies (avelumab, durvalumab, nivolumab, atezolizumab and pembrolizumab) and the exact dosing and treatment schedule will be determined by treatment cycle for each immunotherapy agent.
• The first patient progressed on Keytruda and chemotherapy in first-line NSCLC, and has been dosed with RT, plinabulin (30 mg/m²) and Keytruda.

Plinabulin, a selective immunomodulating microtubule-binding agent (SIMBA), induces maturation of dendritic cells (antigen-presenting cells or APCs) resulting in the activation of tumor antigen-specific T-cells to selectively target cancer cells. It has been demonstrated to revert resistance to PD-1/PD-L1 mAb with an objective response rate of 43% when combined with checkpoint inhibitors in a Phase 1 SCLC study, will be presented at 9 a.m. ET on June 4, 2021 at the ASCO Lung Cancer Poster Session (Abstract #8570) (link). This triple combination regimen is supported by data including >80% tumor reduction in PD-1 mAb non-responsive tumor models as presented at AACR in June 2020. Additionally, recent data, published in Frontiers in Oncology¹, has shown that plinabulin elicits a strong anti-cancer immune response, which polarizes macrophages and increases the ratio of M1-like/M2-like tumor-associated macrophages, further strengthening the support for the anti-tumor immune effects of plinabulin.

“This marks another important step in the continued effort to develop plinabulin franchise as a potential ‘cornerstone’ agent in combination with checkpoint inhibitors for potential synergistic anti-cancer effect. This is another significant milestone after the recent success of Plinabulin combined with PD-1 and CTLA-4 inhibitors with 43% ORR in patients who failed checkpoint inhibitors with durable treatment effect in Phase 1 SCLC study,” said Dr. Ramon Mohanlal, EVP of R&D, CMO of BeyondSpring. “We are excited to advance this clinical study in the hopes of providing patients with a combination therapy option that has the potential to have a significant impact on clinical outcomes and to treat patients who failed checkpoint inhibitors in multiple cancers, a severely unmet medical need.”

For more information on this trial (NCT04902040), please visit clinicaltrials.gov.

1. Natoli M. et al. Plinabulin, a Distinct Microtubule-Targeting Chemotherapy, Promotes M1-Like Macrophage Polarization and Anti-tumor Immunity, Front. Oncol. 11: 644608 (2021)

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. US FDA granted priority review for Plinabulin and G-CSF combination for CIN prevention with a PDUFA date of November 30, 2021. 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) Phase 3 study. 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.

Investor Contact:
Ashley R. Robinson
LifeSci Advisors, LLC
+1 617-430-7577
arr@lifesciadvisors.com

Media Contact:
Darren Opland, Ph.D.
LifeSci Communications
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