BeyondSpring Announces New Analyses of DUBLIN-3 Phase 3 Study Showing Survival Benefit of Plinabulin + Docetaxel in Post Anti-PD-(L)1 for Non-squamous EGFR WT NSCLC and a Reduction in Brain Metastasis Compared to Docetaxel at NACLC 2025

Rhea-AI Summary

BeyondSpring (NASDAQ: BYSI) reported post-hoc DUBLIN-3 analyses showing that plinabulin + docetaxel improved outcomes versus docetaxel in non-squamous EGFR wild-type NSCLC patients after progression on anti-PD-(L)1 therapy.

Key metrics in the subset: median OS 15.8 vs 11.7 months (HR=0.55), PFS 5.6 vs 3.8 months (HR=0.67), ORR 18.2% vs 8.0%. Metastasis-free survival improved to 15.34 vs 7.7 months (HR=0.52, p=0.0012) and new brain metastasis incidence fell to 4.32% vs 7.83%. Safety signals included a reduction in grade 4 neutropenia (5.13% vs 33.58%, p<0.0001) and fewer exposure-adjusted grade 3/4 AEs (p=0.0235). BeyondSpring plans a global registrational Phase 3 DUBLIN-4 to confirm these findings.

Positive

• Median OS improved to 15.8 vs 11.7 months (HR=0.55)
• Median PFS improved to 5.6 vs 3.8 months (HR=0.67)
• ORR increased to 18.2% vs 8.0%
• Metastasis-free survival 15.34 vs 7.7 months (HR=0.52, p=0.0012)
• New brain metastasis reduced to 4.32% vs 7.83%
• Grade 4 neutropenia reduced to 5.13% vs 33.58% (p<0.0001)

Negative

• Results derive from a post-hoc subset analysis, not a prospective primary endpoint

Key Figures

Median OS 15.8 vs 11.7 months DUBLIN-3 post-hoc subset, Plinabulin+docetaxel vs docetaxel (HR=0.55)

Median PFS 5.6 vs 3.8 months DUBLIN-3 post-hoc subset, Plinabulin+docetaxel vs docetaxel (HR=0.67)

Objective response rate 18.2% vs 8.0% DUBLIN-3 post-hoc subset, Plinabulin+docetaxel vs docetaxel

Metastasis-free survival 15.34 vs 7.7 months DUBLIN-3 ITT EGFR WT NSCLC (HR=0.52, p=0.0012)

New brain metastasis 4.32% vs 7.83% DUBLIN-3 ITT, Plinabulin+docetaxel vs docetaxel alone

Grade 4 neutropenia 5.13% vs 33.58% DUBLIN-3, docetaxel-induced neutropenia reduction (p<0.0001)

Grade 3/4 AEs p=0.0235 Significant decrease in exposure-adjusted grade 3/4 adverse events

ITT population size N=559 DUBLIN-3 EGFR WT NSCLC intent-to-treat population

Market Reality Check

$2.18 Last Close

Volume Volume 22,432 is slightly above 20-day average of 20,317. normal

Technical Price $2.02 is trading above 200-day MA at $1.88, after a 4.12% daily gain.

Peers on Argus

BYSI gained 4.12% while peers were mixed: IMMX +2.44%, OSTX +1.02%, ALGS +2.26% vs. ACET -3.07%, IGMS -2.31%, suggesting a stock-specific move.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 12	Earnings and update	Positive	-3.6%	Q3 2025 results, NSCLC data, SEED divestiture progress and cash update.
Aug 13	Earnings and update	Positive	-0.5%	Q2 2025 results plus promising Plinabulin NSCLC combo and SEED progress.
Jul 07	Clinical trial data	Positive	+1.8%	Med (Cell Press) publication showing Plinabulin-driven responses after ICI failure.

Pattern Detected

Recent earnings and clinical updates often showed muted or negative immediate price reactions, with some divergence on positive news.

Recent Company History

Over the past six months, BeyondSpring has highlighted Plinabulin’s clinical profile alongside lean operating spending. On Aug 13, 2025 and Nov 12, 2025, earnings updates paired modest quarterly losses and cash levels with encouraging NSCLC data and SEED Therapeutics milestones, yet shares fell slightly (-0.5% and -3.64%). A Jul 7, 2025 Med (Cell Press) publication of Plinabulin-driven dendritic cell maturation in checkpoint‑refractory cancers saw a smaller +1.79% move. Today’s NACLC Phase 3 post‑hoc DUBLIN‑3 analyses extend that NSCLC narrative with survival, brain metastasis, and safety signals.

Market Pulse Summary

The stock moved +7.9% in the session following this news. A strong positive reaction aligns with evidence that clinical trial news has historically moved BYSI shares by about 3.04%, while today’s gain of 4.12% followed detailed Phase 3 DUBLIN‑3 post‑hoc data. The market previously showed smaller responses to favorable Plinabulin updates, so a larger move could reflect the granularity of survival, metastasis and safety metrics. Investors watching sustainability might consider prior patterns where earnings‑linked news saw negative follow‑through despite clinical momentum.

Key Terms

progression-free survival medical

"showed consistent and clinically meaningful improvements in OS, PFS, and ORR"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

objective response rate medical

"Median progression-free survival (PFS): DP 5.6 vs. D 3.8 months (HR=0.67),Objective response rate (ORR):"

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

metastasis-free survival medical

"Meaningful improvement in metastasis-free survival: Metastasis-free survival improved to 15.34 months"

Metastasis-free survival is the length of time after treatment during which a patient shows no signs that cancer has spread to other parts of the body. For investors, it’s a key clinical measure of a drug’s effectiveness — like how long a repair keeps a leak from returning — because longer metastasis-free survival can improve chances of regulatory approval, support stronger sales forecasts, and reduce future treatment costs.

neutropenia medical

"Plinabulin significantly reduced docetaxel-induced grade 4 neutropenia (5.13% vs. 33.58%, p<0.0001)."

Neutropenia is a medical condition where the blood has an unusually low number of neutrophils, the white blood cells that act like the body’s front-line security guards against bacterial and fungal infections. For investors, it matters because neutropenia can signal safety or tolerability problems for drugs or treatments, driving clinical trial setbacks, regulatory scrutiny, additional monitoring costs, or label warnings that can influence a company’s commercial outlook and stock value. Monitoring for neutropenia is a common part of assessing medical risk and long-term financial impact.

dendritic-cell maturation medical

"These benefits reflect Plinabulin’s first-in-class dendritic-cell maturation mechanism, which helps"

Dendritic-cell maturation is the process by which immature immune cells develop the ability to recognize and display pieces of pathogens or tumor cells to other immune cells, effectively 'teaching' the body what to attack. For investors, this matters because successful maturation is a key sign that vaccines or immunotherapies can trigger a strong, targeted immune response, affecting clinical trial results, regulatory approval prospects, and commercial potential.

non-small cell lung cancer medical

"non-squamous (NSQ) non-small cell lung cancer (NSCLC) who progressed after anti-PD-(L)1"

A broad category of lung tumors that grow from the cells lining the airways and make up the majority of lung cancer cases; it includes several subtypes that behave and respond to treatment differently, like different models of the same car family. It matters to investors because its large patient population and variety of treatment options — surgery, traditional chemo, targeted drugs and immunotherapies — create major markets where clinical trial results, drug approvals or changing treatment guidelines can quickly affect a company’s revenue and stock value.

egfr wild-type medical

"patients with EGFR wild-type (WT) non-squamous (NSQ) non-small cell lung cancer"

EGFR wild-type describes cells or a tumor that carry the normal, unmutated version of the epidermal growth factor receptor (EGFR) gene. For investors, this matters because many targeted cancer drugs and clinical trials are designed to work only when EGFR is mutated; if a patient population is EGFR wild-type, those therapies are less likely to work, which affects drug sales, trial outcomes, regulatory decisions and the size of the addressable market for precision medicines.

nda regulatory

"DUBLIN-4, together with DUBLIN-3, is expected to support a future NDA submission"

An NDA, or nondisclosure agreement, is a legal contract that keeps certain information private between parties. It’s like a promise not to share sensitive details, helping protect business ideas, strategies, or data from being leaked or used without permission. For investors, NDAs help ensure that confidential information remains secure, enabling trust and open communication during business discussions.

AI-generated analysis. Not financial advice.

• 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.
  

 “Patients who relapse after anti-PD-(L)1 therapy represent one of the most significant unmet needs in NSCLC, with docetaxel as the only treatment option while multiple late-stage clinical trials have failed to improve upon it,” said Dr. Trevor Feinstein.

Dr. Lan Huang, Co-Founder, Chairman, and CEO of BeyondSpring, said, “These new analyses suggest Plinabulin’s unique ability to potentially reinvigorate anti-tumor immune function and improve outcomes in patients who have developed resistance to checkpoint inhibitors. The post-hoc analysis data from DUBLIN-3 are consistent with our findings from the prospective 303 study in similar patients, as presented at the Society for Immunotherapy of Cancer (SITC) 2025 Annual Meeting. The observed reductions in brain metastasis and the substantial improvement in metastasis-free survival further highlight Plinabulin’s differentiated clinical profile. These findings provide strong momentum as we move forward with our global confirmatory Phase 3 DUBLIN-4 trial.”

About Plinabulin
Plinabulin is a first-in-class, brain-penetrating, dendritic -cell maturation small molecule.  It has been used in over 700 cancer patients, with good tolerability and showed durable anti-cancer benefit across multiple clinical studies. As a reversible binder at a distinct tubulin pocket, plinabulin does not change tubulin dynamics or antagonize tubulin stabilizing agents, such as docetaxel, which contributes to its differentiated activity and tolerability compared to other tubulin binders. In addition, plinabulin significantly reduces chemotherapy-induced neutropenia and could thereby increase docetaxel tolerability.

About DUBLIN-3 Study (103 Study)
DUBLIN-3 (n=559, NCT02504489) was a multicenter, single-blinded (patient) and randomized, phase 3 trial in 58 medical centers (US, China, and Australia). Only patients with EGFR wild-type NSCLC who had progressed after first-line platinum-based therapy were enrolled. Patients were randomized (1:1) to receive docetaxel (75 mg/m²) on Day 1 and either plinabulin (30 mg/m²) or placebo on Days 1 and 8 in 21-day cycles until progression, unacceptable toxicity, withdrawal, or death. Treated patients were included in the safety analysis and ITT population in the primary efficacy analyses. The primary endpoint for the study was OS, and secondary endpoints were PFS, ORR, Duration of Response (DoR), Grade 4 neutropenia and Quality of Life. The study was published in Lancet Resp Med 12:775, 2024.

About BeyondSpring
BeyondSpring (NASDAQ: BYSI) is a clinical-stage biopharmaceutical company developing first-in-class therapies addressing high unmet medical needs. Its lead asset, Plinabulin, is in late-stage clinical development as an anti-cancer agent in NSCLC and other indications. Plinabulin’s novel mechanism as a dendritic cell maturation agent supports both anti-cancer activity and immune modulation, offering a unique approach to resensitizing tumors resistant to checkpoint inhibitors. Learn more at https://beyondspringpharma.com.

Investor Contact: IR@beyondspringpharma.com
Media Contact: PR@beyondspringpharma.com

FAQ

What did BeyondSpring (BYSI) announce about DUBLIN-3 results on Dec 11, 2025?

BeyondSpring reported post-hoc DUBLIN-3 analyses showing plinabulin + docetaxel improved OS, PFS, ORR and reduced brain metastasis versus docetaxel in EGFR WT non-squamous NSCLC after anti-PD-(L)1.

How much did plinabulin + docetaxel improve median overall survival in DUBLIN-3 (BYSI)?

Median OS was 15.8 months with plinabulin + docetaxel versus 11.7 months with docetaxel (HR=0.55) in the reported subset.

What is BeyondSpring’s next regulatory step after the DUBLIN-3 analyses for BYSI?

BeyondSpring plans a global, double-blind Phase 3 registrational trial DUBLIN-4 following an End-of-Phase 2 meeting with the U.S. FDA.

Did DUBLIN-3 show any safety advantages for plinabulin (BYSI)?

Yes; DUBLIN-3 reported reduced docetaxel-induced grade 4 neutropenia (5.13% vs 33.58%, p<0.0001) and fewer exposure-adjusted grade 3/4 AEs (p=0.0235).

How did plinabulin affect brain metastasis rates in the DUBLIN-3 analyses for BYSI?

New brain metastasis incidence was reported as 4.32% with plinabulin + docetaxel versus 7.83% with docetaxel.

Are the reported DUBLIN-3 findings definitive for approval of plinabulin (BYSI)?

No; the reported benefits are from a post-hoc subset analysis and BeyondSpring intends to confirm results with the planned global Phase 3 DUBLIN-4 trial.