BeyondSpring Publishes Human Clinical Study in Med (Cell Press) Showing Plinabulin-Driven Dendritic Cell Maturation and Tumor Response After Prior Checkpoint Inhibitor Failure

FLORHAM PARK, N.J., July 07, 2025 (GLOBE NEWSWIRE) --BeyondSpring Inc.(NASDAQ: BYSI)today announced publication of a human clinical study inMed(Cell Press) demonstrating thatPlinabulin,when combined with radiation and a checkpoint inhibitor, induces dendritic cell (DC) maturation and elicits tumor responses in patients across multiple cancer types who had failed prior ICI therapy. The study also identified a potential biomarker—baseline GEF-H1 immune signature—that may enable patient pre-selection and clinical response prediction.

“These results offer early but important signals that Plinabulin’s dendritic cell maturation mechanism could play a pivotal role in reversing ICI-acquired resistance,” said Dr. Steven Lin, M.D., Ph.D., corresponding author and Professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center. “The ability of Plinabulin to activate the immune system in this setting is both scientifically intriguing and clinically promising—particularly given the durability of responses in some heavily pretreated patients.”

Dr. Lin added, “It is especially noteworthy that Plinabulin combination demonstrated the best responses innon-small cell lung cancer, head and neck squamous cell carcinoma, and Hodgkin lymphoma.”

“This study builds upon the seminal work of Nobel Laureate Dr. Ralph Steinman and Dr. Ira Mellman, who helped define the essential role of dendritic cells in immune activation,” said Lan Huang, Ph.D., Co-Founder, Chairman, and CEO of BeyondSpring. “Plinabulin’s ability to drive dendritic cell maturation and induce immune responsiveness offers a potential breakthrough strategy for patients who are refractory or relapsed on checkpoint inhibitors. We are committed to advancing Plinabulin’s development in partnership with pioneering cancer research institutions like MD Anderson.”

This investigator-initiated, Phase 1 translational trial (NCT04902040) evaluated a triple immunotherapy approach combining Plinabulin, radiation (RT), and anti-PD-1 checkpoint inhibitors in patients with eight cancer types who are refractory or relapsed on prior ICI therapy. RT was administered only during the first cycle. The primary endpoint was tumor response in non-irradiated lesions.

Lin S.H., Subbiah V., Cohen E.N. et al. “Plinabulin following radiation enhances dendritic cell maturation and checkpoint inhibitor retreatment of relapsed/refractory cancers.”Med. Published June 27, 2025. (https://www.cell.com/med/abstract/S2666-6340(25)00179-5)

This open-label, single-arm Phase 1 basket study (NCT04902040) at MD Anderson Cancer Center investigates safety and efficacy of Plinabulin plus radiation and PD-1 inhibitor in patients refractory or relapsed after prior immunotherapy. The primary endpoint is investigator-assessed ORR (RECIST 1.1) in non-irradiated lesions; secondary endpoints include DCR.

Plinabulin is a first-in-class dendritic cell maturation agentthat binds reversibly to a unique site on tubulin, destabilizing microtubules in a controlled manner to release GEF-H1 (Chem 2019; Cell Reports 2019). Immune protein GEF-H1 activates the RhoA/ROCK signaling pathway, promoting dendritic cell maturation and anti-tumor T-cell immunity. This mechanism is distinct from traditional tubulin agents and does not interfere with tubulin stabilizers like docetaxel.

Across multiple clinical studies andapproximately 800 patients, Plinabulin has shown durable anti-cancer activity and a favorable safety profile, and has significantly reduced chemotherapy-induced neutropenia, potentially enhancing docetaxel tolerability.

BeyondSpring (NASDAQ: BYSI) is a clinical-stage biopharmaceutical company developing first-in-class therapies for high unmet medical needs. Its lead asset, Plinabulin, is inlate-stage clinical development as an anti-cancer agent in NSCLC and a range of cancer indications. Plinabulin’s novel mechanism of action as a dendritic cell maturation agentsupports both anti-cancer activity and immune modulation,offering a unique approach to resensitizing tumors to prior failure or progression to checkpoint inhibitors.

In addition, BeyondSpring is the founding equity holder of SEED Therapeutics, a biotechnology company pioneering targeted protein degradation (TPD) through the discovery of novel molecular glues and bifunctional degraders. Powered by its proprietary RITE3™ platform, SEED is advancing a pipeline of first-in-class degraders to address traditionally undruggable targets across oncology, neurodegeneration, immunology, and virology. SEED’s strategic collaborations with Eli Lilly and Company and Eisai Co., Ltd. support its mission to develop transformational therapies. Learn more atbeyondspringpharma.com.