April 2026
NASDAQ: BYSI Non-Confidential
Investment Highlights
>700 cancer patients treated with good tolerability; Demonstrated overall survival benefits and reduction of severe neutropenia in 2L/3L NSCLC EGFR Wide Type vs. docetaxel
Durable Anti-cancer Efficacy and Safety
First-in-class small molecule: a unique, reversible tubulin depolymerizing agent with MoA of dendritic cell maturation and prevention chemotherapy induced neutropenia
Plinabulin: Unique Immune Modulator
Promising efficacy data in ICI (immune checkpoint inhibitor) combos in patients
with various cancer types after immune checkpoint inhibitors (ICI)-failure
Efficacy Potential in
ICI Failed Patients
SEED: Robust pipeline with lead oncology asset, an oral RBM39 degrader
entered phase 1 study; Investments and R&D Collaborations from Eli Lilly & Eisai
SEED: Novel TPD
Platform & Pipeline
Strong Global Patent Protections for Plinabulin and SEED Platform & Pipeline
Intellectual Property
Post-ICI Landscape: Severe Unmet Medical Need
Immune Checkpoint Inhibitors (ICIs) Have Transformed Cancer Care60%
Progress on ICI
No effective therapies post-ICI
Around US$60B/year Success Story with a Critical Gap
Approved in 20+ cancer types
Nearly $60B in global annual sales
Have redefined first-line treatment in NSCLC and other solid tumors
Current Options are Limited and Toxic>60% patients develop "acquired resistance" due to T cell exhaustion and/or antigen presenting cell (APC) pathway alterations.1 After progression, ICIs are no longer recommended alone owing to limited efficacy
Current limited options include chemotherapy, which is associated with severe neutropenia
Urgent OpportunityNo newly approved therapies specifically address ICI resistance/progression
Significant clinical and commercial opportunity
Memon et al. Cancer Cell 42, 209-224 (2024).
Plinabulin: Unique Dual Mechanism with Immune and Safety Benefits
Reversible tubulin binder - distinct from taxanes, vincas, or colchicine; does not disrupt microtubule dynamics
Immune modulation - induces dendritic cell maturation and primes T cells by activating GEF-H1
Neutropenia mitigation - reduces chemotherapy-induced neutropenia by stimulating GMP progenitor cells
Positive benefit/risk Ratio: improve anti-cancer efficacy and tolerability in combination therapy
Plinabulin, a Differentiated Late-Stage Oncology Asset with Broad Potential
Robust clinical foundation: >700 cancer patients treated with good tolerability.
Unique MoA: Brain-penetrating, reversible tubulin binder driving dendritic cell maturation and T cell activation (Chem 2019, Cell Reports 2019, Med 2025); reduces chemotherapy-induced neutropenia (JAMA Oncology 2020). Synergizes with Chemo, ADC, radiation, and checkpoint inhibitors.
Extended patent protection: Composition of Matter (NCE) patent protection to 2036; Likely
patent extension to 2041 based on Hatch-Waxman Act.
Validated benefit: Dublin-3 Phase 3 trial (n=559) demonstrated significant OS, PFS, ORR improvement with durable long-term survival benefits and significant reduction in grade 4 neutropenia in "Plinabulin + Docetaxel" vs Docetaxel in 2L/3L NSCLC EGFR WT (LANCET RM 2024).
Regulatory momentum: Per productive discussions with US FDA and EMA, we are in late-stage clinical development in non-squamous NSCLC after progression on PD-1/L1 inhibitors (Dublin-4 study), which is MoA-targeted, homogeneous and high-need patient group.
Plinabulin Monohydrate is a Brain-Penetrant, Unique Tubulin Depolymerizing
Agent which induces "Dendritic Cell or DC Maturation via GEF-H1 release"
Plinabulin Monohydrate is a unique tubulin binder1
Plinabulin release GEF-H1 from microtubule, activates RhoA/ROCK pathway, leading to DC Maturation2,3
In WT DC cells, plinabulin can induce DC maturation, but not in GEF-H1 deleted DC cells2
1. La Sala et al., Chem 5(11): 2969-2986 (2019); 2. Kashyap et al., Cell Reports 28(13): 3367-3380 (2019); 3. Choi et al. Cell 189 (2): 461-477 (2026)
Plinabulin Displays GEF-H1-mediated Mechanism-of-Action
By depolymerizing microtubules, plinabulin activates GEF-H1, a C1 domain-associated RhoA activator, in a highly regulated and spatio-temporal dependent manner.1
As a GEF-H1 agonist, plinabulin has the
following anti-cancer mechanism:
GEF-H1 activates RhoA/ROCK signaling pathway and leads to DC maturation/M1 polarization and T-cell activation, which has been validated in preclinical and clinical studies.2-4
GEF-H1 promotes proliferation of HSPCs biasing towards the GMP lineage during productive hematopoiesis, contributing to Plinabulin CIN prevention benefit.5-7
Due to GEF-H1's role in vasculature, plinabulin
modulates angiogenesis.8-9
1. Choi SR (2026) Cell 189(2):461; 2. La Sala G (2019) Chem 5(11):2969; 3. Kashyap AS (2019) Cell Rep 28(13):3367; 4. Lin SH (2025) Med 10(6):100752; 5. Tonra JR (2020) Cancer Chemother Pharmacol
85:461; 6. Blayney DW (2020) JAMA Oncol 6(11):e204429; 7. Chan DCH (2021) Blood Advances 5(16):3120; 8. Mita MM (2010) Clin Cancer Res. 16(23)1; 9. Risinger AL (2025) EMBO Mol Med 17(5):866.
Plinabulin-Responding Patients After ICI Failure Show Immune Activation Evidenced by Rapid DC Maturation in the Peripheral Blood
In 8 Cancers failed prior ICI, Plinabulin
combination with disease control rate of 54%1
CCR7, CD80 and CD83 are rapidly upregulated at cycle 1 Day 4
in responding (PR + SD) patients1
Dendritic Cell Maturation & Migration
1. Lin et al., Med 6(10):100752 (2025)
Non-Confidential
9
Plinabulin Improves Anti-cancer Efficacy and Increases Tolerability of Dato-DXd (TROP2-TOP1 ADC) with Increased CD8+ T cell/Treg Ratio (AACR 2026)
Plinabulin significantly improves complete response rate and survival of ADC
with or without PD-1 Inhibitor
Tumor Volume (mm3)
3000
2500
2000
1500
1000
500
Vehicle control
Tumor Volume (mm3)
3000
2500
2000
1500
1000
500
Dato-DXd
CR: 0/10
Tumor Volume (mm3)
3000
2500
2000
1500
1000
500
Pembrolizumab
100
%Survival
80
60
40
Survival outcome
(non-tumor related deaths censored)
Vehicle control
Dato-DXd (5 mg/kg, QW)
Pembrolizumab (0.3 mg/kg, Q3D) Dato-DXd + Pembrolizumab
Dato-DXd + Plinabulin (7.5 mg/kg, BID on D1 + BIW)
0
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Days
Dato-DXd+Pembrolizumab*
0
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Days
Dato-DXd + Plinabulin
0
CR: 0/10
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Days
50
0
Dato-DXd
Pembrolizumab (Pembro) Plinabulin (Plin)
Dato-DXd+Pembro Dato-DXd+Plin
Dato-DXd+Pembro+Plin
100
ns
150
ns
ns
*
200
***
**
250
Vehicle control
✱ ✱✱
✱
300
Day 7 (blood): CD8 T/Treg Ratio
✱✱
✱
Dato-DXd+Pembrolizumab+Plinabulin**
20
0
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Days since First Administration
Dato-DXd + Pembrolizumab + PlinabulinTumor Volume (mm3)
3000
2500
2000
1500
1000
500
CD8/Treg frequency ratio
0
CR: 5/10
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Days
3000
Tumor Volume (mm3)
2500
2000
1500
1000
500
0
CR: 2/10
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Days
3000
Tumor Volume (mm3)
2500
2000
1500
1000
500
0
CR: 6/10
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Days
Plinabulin shifts tumor microenvironment to Immune Active by increasing CD8+ T cell/T reg ratio
*4/10 animals found dead
No animal death **1/10 animals found dead
hTROP2-MC38 colorectal cancer in hPD-1 mice
Plinabulin's Immunomodulation and Neutropenia-Mitigating Activities Position it as a Valuable Addition for Combination Regimens
Tumor Vasculature
Plinabulin targets
tumor vasculature
Plinabulin induces
DC maturation +
M1 Polarization
Improves safety*
Plinabulin reduces chemotherapy-induced neutropenia
Antigen Presenting Cell (APC)
Enhanced antigen presentation and T cell priming
Vascular Normalization
Improved therapeutic index of chemotherapy-based regimens
Target Acquired Resistance to ICI;
Antigen Presentation, Boost T cell function, Kill tumor cells, and Normalize vasculature
Extends chemo therapeutic
duration and improves anti-
cancer benefit
Plinabulin Clinical Studies in Multiple Cancers
>700 cancer patients treated with Plinabulin with good tolerability
Indication/Target | Program | Preclinical | Phase 1 | Phase 2 | Phase 3 | Registration | Trial Name / Collaborator | |
Late stage | NSCLC (2nd/3rd line) | Plinabulin + Docetaxel | Study 103 (DUBLIN-3) - OS, PFS, ORR benefit 1 | |||||
CIN Prevention | Plinabulin alone or + Pegfilgrastim | Studies 105 & 106 2, 3 (PROTECTIVE-1 & PROTECTIVE-2) | ||||||
NSCLC (2L/3L) progressed on PD-1/L1 Inhibitor | Plinabulin + Pembrolizumab + Docetaxel | Study 303 | ||||||
ES-SCLC (1L) | Plinabulin + Pembrolizumab + Etoposide / Platinum | Study 302 | ||||||
Eight types of cancers Failed PD-1/L1 Inhibitor | Plinabulin + PD-1/PD- L1 + Radiation | 4 | ||||||
Breast Cancer | Plinabulin + ADC with topoisomerase inhibitors (TOP1-ADC) |
Mechanisms not restricted to lung cancer; other solid tumors may benefit, with early signals in liver, head and neck, prostate, breast, and ES-SCLC.
1. Han et al., Lancet Resp Med 12(10): 775-786 (2024), 2. Blaney et al. JAMA Oncol 6(11): e204429 (2020);
3. Blaney et al. JAMA Network Open 5(1): e2145446 (2022); 4. Lin et al., Med 6(10):100752 (2025)
Post-ICI NSCLC: A Large, Growing and Unmet Clinical Challenge
Limited treatment options after PD-1/L1 inhibitor progression
Chemotherapy remains the main option, with poor outcome and high toxicity
Urgent need for differentiated therapy with immune re-sensitization
Docetaxel Remains a Global Standard of Care (SOC) in Post-ICI NSCLC, EGFR WT, Despite Limited Benefit and Substantial Toxicity
Current Standard of Care
Docetaxel Overview
Approved >25 years ago
Remains the NCCN-recommended standard of care for 2L/3L NSCLC with no targetable alterations
Used after progression on anti-PD-(L)1 antibody
± chemotherapy
Used in real world practice across U.S., EU, Japan, and China
Limitations
Median OS: ~9-11 months
40% experience severe neutropenia
Industry-wide Phase 3 Trials Summary
11 Phase 3 Studies with no OS Benefit vs. Docetaxel
7 global trials including ADCs and anti-PD-(L)1
combos did not improve OS vs. docetaxel ¹
#8 failed global trial PRAGMATICA-LUNG (SWOG S2302) - ASCO 2025 2
N=838, randomized 1:1, Ramucirumab + pembrolizumab (mOS 10.1 Mo) vs. SOC (mOS 9.3 Mo), HR 0.99, p=0.46
#9 failed global trial COSTAR (GSK) - 07/2025
N=758, TIM-3 + PD-1 + docetaxel vs. PD-1 + docetaxel vs. docetaxel. Triple combo & combo did not improve OS vs. docetaxel
#10 failed global trial LATIFY (AZ) - 12/2025
N=594, Durvalumab + Ceralasertib (ATR
inhibitor) did not improve OS vs. docetaxel.
#11 Prgm ended ABBIL1TY (Genmab) - 12/2025
N=702, Acasunlimab (PD-L1x4-1BB) +
1. Malinou J et al., ASCO 2024; 2. Dragnev KH etal. ASCO 2025
pembrolizumab vs Docetaxel
"Plinabulin and Docetaxel" Demonstrated Significant OS benefit vs. Docetaxel in a Global
Phase 3 Study with Stage IIIb/IV NSCLC EGFR WT Patients (Dublin-3, n=559)
Docetaxel + Plinabulin vs. Docetaxel + Placebo in Patients with EGFR Wild-Type NSCLC
Global, randomized, single-blinded (to patients)
Stratified by region (Asia/non-Asia), prior line (2L or 3L), ECOG (0-1/2), Prior PD-1/PD-L1
(yes/no)
Overall survival
(OS)
Primary endpoint
Study Plan
DoR
Q-TWiST; QoL
Proportion of patients who received docetaxel >8 cycles, >10 cycles and
>12 cycles
ORR, PFS
Percent of patients without severe neutropenia (Day 8, cycle 1)
Month 24 and 36 OS rate
Secondary endpoints
DP:
Docetaxel
(75 mg/m2, day 1)
+ Plinabulin
(30 mg/m2, day 1, 8)
Inclusion Criteria:
Non-squamous or squamous NSCLC
Stage IIIb/IV
ECOG ≤ 2
Progression during or after treatment with one or two treatment regimens containing a platinum
Must have at least one measurable lung lesion
Prior checkpoint inhibitor therapy allowed
N=559
R
D:
Docetaxel
(75 mg/m2, day 1)
+ Placebo (day 1, 8)
1:1 ratio
21-day per cycle
Plinabulin IV Infusion: 1 or 2 dose per cycle
Publication: Lancet Respir Med 12(10): 775-786 (2024)
Plinabulin + Docetaxel vs. Docetaxel (n=559) Met its Primary Endpoint of OS and Secondary Endpoints of PFS, ORR, and Grade 4 Neutropenia Reduction
Grade 4 neutropenia, All Cycles Day 8
Plinabulin Significantly Reduced Grade 4 neutropenia of Docetaxel
Plinabulin and Docetaxel Showed Significant Improvement in Long-term OS Rate
- Double 2-year, 3-year OS Rate
OS HR=0.82
Log rank p=0.0399
P<0.0001 | ||
33.58% | ||
5.13% | ||
50%
Percentage of Patients
40%
30%
20%
10%
Mean OS (SE) | Median OS (95% CI) | HR | |
Docetaxel | 12.77 (0.676) | 9.4 (8.4, 10.7) | |
Plinabulin + Docetaxel | 15.05 (0.848) | 10.5 (9.3, 11.9) | 0.82 (0.68, 0.99) |
Publication: Lancet Respir Med 12(10): 775-786 (2024)
0%
Docetaxel +
Similar results for Grade 4 neutropenia on Cycle 1 Day 8
- Day 8 is ANC Nadir for Docetaxel
Placebo
Docetaxel +
Plinabulin 30 mg/m2
Plinabulin + Docetaxel (DP) is Safer Than Docetaxel (D) Adjusted by Exposure
The combination has Significant lower Grade 3 or 4 exposure-adjusted event rates vs. Docetaxel
Grade 3 or 4 Event Rates Adjusted by Exposure | Grade 4 Only Event Rates Adjusted by Exposure | |||
DP (n=274) | D (n=278) | DP (n=274) | D (n=278) | |
Descriptive Statistics | ||||
Number of patients with events, n (%) | 203 (74·1) | 212 (76·3) | 61 (22·3) | 121 (43·5) |
Total number of years of dose regimen | 83·43 | 71·65 | 83·43 | 71·65 |
Total number of events | 814 | 783 | 141 | 221 |
Observed event rate per year | 9·76 | 10·93 | 1·69 | 3·08 |
Estimated event rate per year (95% CI) | 9·76 (9·11, 10·45) | 10·93 (10·19, 11·72) | 1·69 (1·43, 1·99) | 3·08 (2·70, 3·52) |
Treatment Difference | ||||
RR vs Docetaxel + Placebo (95% CI) | 0·89 (0·81, 0·98) | 0·55 (0·44, 0·68) | ||
P-value vs· Docetaxel + Placebo | 0·0235 | <0·0001 | ||
Plinabulin and Docetaxel Combo arm had more cycles of treatment vs. Docetaxel alone.
Publication: Lancet Respir Med 12(10): 775-786 (2024)
Dublin-3: Post-hoc Analysis in Plinabulin Mechanism-Based Population in
2L/3L Non-squamous EGFR WT NSCLC and Progressed on PD-1/L1 Inhibitors
Non-squamous
mOS extension of 2.5 months
(DP 11.4 vs. D 8.8 months, HR 0.72)
Non-squamous, progressed on ICI (Plinabulin MoA-enriched population)
mOS extension of 4.1 months (DP 15.8 vs. D 11.7 months, HR 0.55)
OS HR=0.72
Log rank p=0.0078
OS HR=0.55
Log rank p=0.076
Non-squamous
N
Median OS (95% CI) HR
Log rank P value
Non-squamous, post-ICI
N
Median OS (95% CI) HR
Log rank P value
Docetaxel 178 8.81 (7.73, 10.65)
Plinabulin +
154 11.37 (9.37, 12.95) 0.72 (0.57, 0.92) P = 0.0078
Docetaxel 25 11.7 (7.59, 13.77)
Docetaxel
Plinabulin + Docetaxel
22 15.8 (9.34, 29.06) 0.55 (0.28, 1.07) P = 0.076
Publication: Lancet Respir Med 12(10): 775-786 (2024)
Study 303 (Plinabulin + Docetaxel + PD-1) in 2L/3L Metastatic NSCLC Progressed on PD-1/L1 Inhibitors Shows Consistent Data as Dublin-3 Analysis
Primary Endpoint (n=47) - SITC 2025 | |
Confirmed ORR（RECIST 1.1） | 18.2% |
Secondary Endpoint | |
Median PFS（RECIST 1.1） | 7.0 months |
Median OS | 16 months+, Not reached |
Median DoR（RECIST 1.1） | 7.2 months |
Disease Control Rate (DCR) | 85.1% |
12 months OS% | 79% |
24 months OS% | 66% |
Best Change (%) in Target Lesions
Median follow-up at data cutoff (30 September 2025) was 14.3 months.
IO Mechanism Support: Whole blood analysis indicated higher proportions of activated CD4+/CD8+ T-cells post treatment.
Clinically Meaningful Efficacy Data: 303 study data almost doubled efficacy vs. historical data of docetaxel in similar patients from TROPOIN LUNG-01 (Thoracic Oncology 43(3): 260-272 (2024)): ORR: 12.8%; mPFS: 3.7
months; mOS: 11.8 months.
Median age was 67 (44-83); 80.9% male and 19.1% female. 72.3% were current or former smokers.
Histology included 63.8% with non-squamous cell carcinoma, 36.2% with squamous cell carcinoma.
Planned Dublin-4 Study As a Confirmatory Phase 3 Study
Plinabulin Mechanism-Enriched Patients
Dublin-4: "Plinabulin + Docetaxel" vs. "Docetaxel" in 2L/3L non-squamous NSCLC, EGFR/ALK/ROSm/RET Wild Type, progressed on PD-1/L1 with PFS ≥ 3 monthsDefined, homogeneous group with clear unmet need and Plinabulin MoA alignment
Scientific RationaleTumor Vasculature Targeting: Plinabulin acts on tumor vasculature → Dublin-3 OS HR 0.72 in non-squamous NSCLC patients. Avastin, a vasculature targeting agent, only approved in non-squamous NSCLC patients.
Immune Re-sensitization: Plinabulin has the potential to overcome ICI "acquired resistance" due to T-cell exhaustion / APC pathway mutation1 by dendritic-cell (DC) maturation MoA. DC is the most potent APC → restores T-cell priming → strengthens the Cancer-Immunity Cycle.
Supporting Clinical Data in NSCLC patients progressed on PD-1/L1 InhibitorsDublin-3 (DP): OS HR 0.55, mOS: 15.8 vs 11.7 months (Plinabulin + docetaxel DP vs docetaxel D), mPFS 5.6 vs. 3.8 months (HR 0.67), ORR 18.2% vs. 8.0%.
303 Study (DP+PD-1): 24-month OS rate 66% (mOS 16 month+), mPFS 7.0 month, ORR 18.2%
1. Memon et al. Cancer Cell 42, 209-224 (2024).
Non-Confidential
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BeyondSpring Inc. published this content on April 22, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 22, 2026 at 22:08 UTC.
