BeyondSpring Presents Final Data Analysis of DUBLIN 3 Phase 3 Study in 2L/3L EGFR Wild type NSCLC at ESMO Congress 2024

• Plinabulin/Docetaxel Combination Demonstrated Favorable Benefit/Risk Ratio over Docetaxel Alone: Significant Improvement in Overall Survival, Progression Free Survival, and Objective Response, with additional Significant Reduction of Grade 4 Neutropenia (>80% relative reduction), and Improved Patients' Quality of Life

Florham Park, N.J., September 16, 2024 - BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company developing innovative cancer therapies, presented final data on Dublin-3 study (2L/3L EGFR wild-type NSCLC) focusing on safety outcomes on September 14, 2024 at European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain. Full data on Dublin-3 study was published on September 9, 2024 in the Lancet Respiratory Medicine (https://doi.org/10.1016/S2213-2600(24)00178-4).

Docetaxel remains the standard of care for patients with 2L/3L NSCLC without targetable alterations despite severe neutropenia (>40%) that greatly impair patients' quality of life. Six recent phase 3 studies in patients with EGFR wild-type NSCLC who were previously treated with immune checkpoint inhibitors failed to show overall survival (OS) benefit compared with docetaxel (SAPPHIRE, LEAP-008, CONTACT01, EVOKE-01, CARMEN-LC03, and CANOPY-2). Two phase 3 studies (LUNAR and TROPION-Lung01) showed positive but mixed outcomes compared with docetaxel.

The DUBLIN-3 study was a multicenter, single-blinded, randomized controlled trial that enrolled patients from 58 medical centers across Australia, China, and the USA. 559 patients with epidermal growth factor receptor (EGFR) wild-type NSCLC were randomly assigned (1:1) to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). The plinabulin/docetaxel combination significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to docetaxel alone. (Click here for related press release.)

This poster presentation focused on plinabulin and docetaxel combination safety vs. docetaxel alone, as shown below:

• The combination is well tolerated: Similar percentages of patients experienced ≥1TEAE (treatment emergent adverse events); 99.6% in the combination arm and 99.3% in the docetaxel arm. There was less grade 4 TEAE in the combination arm (19.0%) vs. 42.8% in the docetaxel arm.
• The combination had >80% relative reduction in Grade 4 neutropenia (p<0.001): The combination arm had a 5.3 % Grade 4 neutropenia in Cycle 1 Day 8 compared to 27.8% in docetaxel alone (81% reduction, p<0.0001). The combination arm had a 5.1 % Grade 4 neutropenia in all cycles Day 8 compared to 33.6% in docetaxel alone (85% reduction, p<0.0001). In addition, hospital admission due to febrile neutropenia was lower in the combination arm (7 [2.6%] patients) vs. docetaxel arm (14 [5.0%] patients).
• The combination had reduced use of granulocyte-colony stimulating factor (G-CSF) in all cycles: Post-hoc analysis showed reduced G-CSF use in the combination arm (152 [56%] patients) vs. docetaxel arm (182 [66%] patients) and at cycles 1 to 4.
• The combination had improved quality-of-life (QoL) based on Q-TWiST data: Exploratory analysis showed better QoL based on Q-TWiST in the combination arm, with a clinically meaningful relative gain to the docetaxel arm of 18.5%(p=0.0393).
• The combination had a significant reduction in cycle-adjusted serious adverse events (SAE): Patients randomized to the combination received more cycles of treatment. When cycles were adjusted for SAEs, plinabulin significantly decreased Grade 3/4 SAEs (p=0.0235) and Grade 4 SAEs (p<0.0001).
• The combination had manageable side effects: Plinabulin induced mostly asymptomatic transient hypertension, which mostly resolved within 4-6 hours after infusion without medication. In addition, plinabulin induced GI side effects, including nausea, vomiting, and diarrhea, which were effectively managed following a protocol adjustment to add the prophylactic use of antiemetics and increase time of infusion.

"NSCLC patients without targetable alterations whose disease has progressed on previous platinum-based therapy have a poor prognosis. Docetaxel is the current standard of care with >40% severe neutropenia and poor quality of life. In second or third-line NSCLC patients with EGFR wild-type, the phase 3 data suggest that adding plinabulin to docetaxel has a favorable benefit/risk ratio compared to docetaxel alone in significantly improving anti-cancer efficacy, and significantly reducing severe neutropenia and improving quality of life. This combination could be considered as a new option for second or third-line NSCLC patients without driver mutation, which is a severe unmet medical need," said Dr. Feinstein, one of the lead principal investigators of Dublin-3 study at Piedmont Cancer Center, Atlanta.

ESMO Congress 2024 Presentation (1358P): Plinabulin/Docetaxel Versus Docetaxel in Survival Benefits of 2L/3L EGFR Wild-Type NSCLC after Platinum Regimens (DUBLIN-3): a Randomized Phase 3 Trial

• Presenter: Trevor M. Feinstein
• Poster Session: NSCLC, metastatic

Citation:

Han B., et al. Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med. 2024 Sep 09: S2213-2600(24)00178-4.

About Plinabulin

Plinabulin is a novel first-in-class dendritic cell (DC) maturation therapeutic with durable anti-cancer benefit observed 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. Importantly, clinical data suggests that plinabulin enhances the cancer immunity cycle when used sequentially with chemotherapy/radiation and a checkpoint inhibitor. In addition, plinabulin significantly reduces chemotherapy induced neutropenia and could thereby increase docetaxel tolerability. Over 700 patients have been treated with plinabulin with good tolerability.

About Dublin-3 Study
Dublin-3 NSCLC was a global phase 3 randomized, controlled clinical trial comparing the combination of plinabulin and docetaxel to an active control arm of docetaxel alone (1:1 randomization) in second- and third-line NSCLC patients who had failed platinum doublet therapies, and who were epidermal growth factor receptor (EGFR) wild-type. Docetaxel was given on Day 1 in both arms at 75 mg/m² in each 21-day cycle. Plinabulin was given on Day 1, one hour after docetaxel, and on Day 8, both at 30 mg/m² in each cycle. 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.

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About BeyondSpring

BeyondSpring is a global clinical-stage biopharmaceutical company developing innovative therapies to improve clinical outcomes for patients with high unmet medical needs. The Company is advancing its first-in-class lead asset, plinabulin, a potent inducer of dendritic cell maturation, in late-stage clinical development as a direct anti-cancer agent in NSCLC and a variety of cancer indications. BeyondSpring's pipeline also includes three preclinical immuno-oncology assets. Additionally, BeyondSpring is an equity owner of SEED Therapeutics, Inc which is a pioneer in Target Protein Degradation technology and its application in innovative drug development. Learn more by visiting https://beyondspringpharma.com.

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