BeyondSpring Announces New Post-Hoc Analyses From Global Phase 3 DUBLIN-3 Study, Showing Plinabulin Plus Docetaxel Provides Clinically Meaningful Benefit For Patients With EGFR WT NSQ NSCLC

• In DUBLIN-3 non-squamous EGFR WT NSCLC patients who progressed after anti-PD-(L)1, Plinabulin + docetaxel showed consistent and clinically meaningful improvements in OS, PFS, and ORR, reinforcing Plinabulin as a late-stage therapy with consistent survival benefit in anti-PD-(L)1-progressed NSCLC patients.
   
• Supported by anti-cancer efficacy and safety in significant reduction exposure-adjusted grade 3/4 adverse events in DUBLIN-3, BeyondSpring will conduct DUBLIN-4, a global, double-blind Phase 3 registrational trial. This study will evaluate Plinabulin + docetaxel vs. docetaxel in non-squamous EGFR wild-type NSCLC after progression on anti-PD-(L)1 and chemotherapy, and is intended to serve as the global confirmatory study.
   

FLORHAM PARK, N.J., Dec. 11, 2025 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ:BYSI), a clinical-stage biopharmaceutical company developing first-in-class immune-modulating cancer therapies, today announced new post-hoc analyses from its global Phase 3 DUBLIN-3 Study (Lancet Resp Med 12:775, 2024), showing that Plinabulin plus docetaxel provides clinically meaningful benefit for patients with EGFR wild-type (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC) who progressed after anti-PD-(L)1 immunotherapy. The findings were presented by Dr. Trevor Feinstein of Piedmont Cancer Center and acting chair of the Lung Disease Group for the OneOncology network at the 2025 IASLC/ASCO North America Conference on Lung Cancer (NACLC).

More than 60% of NSCLC patients eventually develop resistance to anti-PD-(L)1 therapy, yet no new treatments have been approved in a decade. Nine late-stage trials, including ADC and anti-PD-(L)1combination regimens, have failed to show overall survival improvement over docetaxel. Plinabulin is a late-stage therapeutic candidate that has demonstrated consistent survival benefit in this rapidly growing population with major unmet medical need.

In a mechanism-driven, post-hoc subset analysis of DUBLIN-3, non-squamous EGFR WT NSCLC patients who progressed after anti-PD-(L)1 therapy with at least 3 months of prior clinical benefit, Plinabulin + docetaxel (DP) combination showed clinically meaningful improvement compared to docetaxel alone (D).

• Median overall survival (OS): DP 15.8 months vs. D 11.7 months (HR=0.55), 
• Median progression-free survival (PFS): DP 5.6 vs. D 3.8 months (HR=0.67),
• Objective response rate (ORR): 18.2% vs. 8.0%.
   

These benefits reflect Plinabulin's first-in-class dendritic-cell maturation mechanism, which helps to restore antigen presentation and T-cell function after acquired resistance to checkpoint inhibitors.

BeyondSpring plans to initiate a global Phase 3 DUBLIN-4 trial following its End-of-Phase 2 meeting with the U.S. FDA. DUBLIN-4, together with DUBLIN-3, is expected to support a future NDA submission in non-squamous EGFR wild-type NSCLC following progression on anti-PD-(L)1 therapy.

Post-hoc analysis of DUBLIN-3 intent-to-treat (ITT, N=559) EGFR WT NSCLC population showed additional clinically meaningful benefits for the Plinabulin + docetaxel combination compared to docetaxel.

• Meaningful improvement in metastasis-free survival: Metastasis-free survival improved to 15.34 months (DP) versus 7.7 months (D, HR=0.52, p=0.0012), consistent with Plinabulin's DC maturation and durable anti-cancer benefit.
• Reduction in new brain metastasis: The incidence of new brain metastasis was reduced to 4.32% (DP) vs. 7.83% (D), consistent with Plinabulin's brain-penetrant properties which demonstrated survival benefit in glioblastoma anal model as a monotherapy.
   
• Improved safety: Plinabulin significantly reduced docetaxel-induced grade 4 neutropenia (5.13% vs. 33.58%, p<0.0001). Plinabulin combination had significantly decreased exposure-adjusted grade 3/4 adverse events vs. docetaxel (p=0.0235), supporting prolonged treatment exposure and contributing to improved clinical outcomes.