Slide 1: January 2025 | NASDAQ: BYSI
January 2025 | NASDAQ: BYSI
Slide 2: Disclaimer
Disclaimer This presentation has been prepared for informational purposes only. No money or other consideration is being solicited, and if sent in response, will not be accepted. This presentation shall not constitute an offer to sell, or the solicitation of an offer to buy, any securities, nor shal
Slide 3: Investment Highlights
Investment Highlights Plinabulin Favorable > 700 Cancer Patients Treated with Good Tolerability Safety Profile Positive Phase 3 study in 2L/3L NSCLC with Significant Overall Survival Benefit: Anti-cancer Efficacy 1. durable anti-cancer benefit in doubling 2-year, 3-year OS rate 2. enables more chemo
Slide 4: Pipeline
Pipeline Indication/Target Program Preclinical Phase 1 Phase 2 Phase 3 Registration Trial Name / Collaborator Study 103 (DUBLIN-3) NSCLC - Presented at ISLAC, ESMO 2024 Plinabulin + Docetaxel (2nd/3rd line) Published in “LANCET Respiratory Medicine” Late stage 09/2024 Plinabulin + Studies 105 & 106
Slide 5: Sale of a Portion of Equity Interest in SEED to Advance Lead Asset Plinabulin
Sale of a Portion of Equity Interest in SEED to Advance Lead Asset Plinabulin in Anti-Cancer Clinical Development • $35.4 M gross proceeds for non-diluting financing by selling a portion of SEED A-1 shares o Strategically positioned to advance our 303 and 302 Studies in Plinabulin combination with i
Slide 6: Plinabulin: First-in-class Late-Stage Clinical Asset for Cancer Treatment
Plinabulin: First-in-class Late-Stage Clinical Asset for Cancer Treatment 6
Slide 7: First-in-class Asset: Plinabulin
First-in-class Asset: Plinabulin • Positive Phase 3 study in 2L/3L NSCLC, successfully demonstrated significant Anti-cancer OS benefit, doubling 2-year, 3-year OS rate – proving plinabulin’s clinical Clinical Agent utility Target IO Failure • Promising efficacy data in triple IO combo (Plinabulin +
Slide 8: Plinabulin: Addressing Severe Unmet Medical Needs as an Add-on Therapy to Immuno-Oncology Regimens
Plinabulin: Addressing Severe Unmet Medical Needs as an Add-on Therapy to Immuno-Oncology Regimens PD-1/PD-L1 Inhibitors Potential to greatly expand the $50B global annual sales addressable market Current Severe Unmet Medical Needs Plinabulin Clinical Development 2L/3L: PD-1/PD-L1 relapsed/refractor
Slide 9: Plinabulin's Journey: Development Milestones Across 700+ Cancer Patients
Plinabulin’s Journey: Development Milestones Across 700+ Cancer Patients Plinabulin MOA Discovery: Unique Dublin-3 Anti-Cancer Study Tubulin Binder, Induces DC Maturation (Lancet Respiratory Medicine 2024; (Chem 2019; Cell Reports 2019) ISLAC 2024; ESMO 2024) Phase 1a, 1b Study Phase 3 in 2L/3L NSCL
Slide 10: Plinabulin is a Reversible Tubulin Binder with Differential Binding, Clinical Activity and Favorable Safety Profile
Plinabulin is a Reversible Tubulin Binder with Differential Binding, Clinical Activity and Favorable Safety Profile Plinabulin is a reversible tubulin binder and does not alter tubulin dynamics Conventional tubulin binding agents (such as taxanes, vinca alkaloids, and colchicine) alter tubulin dynam
Slide 11: Plinabulin: Induces Innate and Adaptive Immunity via DC Maturation
Plinabulin: Induces Innate and Adaptive Immunity via DC Maturation By depolymerizing microtubules, plinabulin releases, or activates, immune defense protein GEF-H1. This leads to dendritic cell maturation (the most potent APC). In WT DC cells, plinabulin can induce DC maturation, but not in GEF-H1 d
Slide 12: Radiation+anti-PD1+Plinabulin Triple Combination POC in Animals
Radiation (RT)+anti-PD1+Plinabulin Triple Combination POC in Animals Provides Evidence of Plinabulin’s Activity in DC Maturation and T cell Activation Tumor reduction is most robust DC activation is most dramatic in triple I/O combination in triple I/O combination Plinabulin+ RT+PD-1 increased DC ma
Slide 13: MOA PoC in Human: Early Immune Activation Evidenced by Rapid DC Maturation
MOA PoC in Human: Plinabulin-Responding Patients Show Early Immune Activation Evidenced by Rapid DC Maturation in the Peripheral Blood Phase 1b study in a number of IO Relapsed/Refractory solid tumors, DC Eligibility: maturation at cycle 1 Day 4 were observed in plinabulin-responding patients Any ca
Slide 14: Plinabulin Enhances the Cancer Immunity Cycle in Checkpoint Inhibitor-Resistant Patients
Plinabulin Enhances the Cancer Immunity Cycle in Checkpoint Inhibitor- Resistant Patients (CINR) ② Plinabulin 2 Improved antigen presentation ③ Checkpoint Inhibitors Stimulate maturation of dendritic 3 Anti-tumor T cell activation cells to increase antigen presentation; Optimize T cell response DC s
Slide 15: Plinabulin's Immunomodulation and Neutropenia-Mitigating Activities Position it as a Valuable Addition
Plinabulin’s Immunomodulation and Neutropenia-Mitigating Activities Position it as a Valuable Addition for Immuno-Chemotherapy Combination Regimens These aspects result in an optimal scenario of added efficacy with potentially reduced toxicity. Dendritic Cells Tumor Vasculature Improves safety* Plin
Slide 16: Plinabulin Improves Overall Survival and Enhances Safety in 2L/3L NSCLC (Dublin-3 Study)
Plinabulin Improves Overall Survival and Enhances Safety in 2L/3L NSCLC (Dublin-3 Study) • Lancet Respiratory Medicine (publication on Sept 9, 2024) • Oral Presentation at ISLAC 2024 16
Slide 17: 2L/3L NSCLC (No Driver Mutation) Has Been a Historically Difficult Space in Which to Develop
2L/3L NSCLC (No Driver Mutation) Has Been a Historically Difficult Space in Which to Develop Treatment options in 2L/3L NSCLC are limited • Docetaxel-based therapies remains the standard of care in 2L/3L NSCLC (EGFR wild type). No new therapy approved in the last 10 years. • However, docetaxel-based
Slide 18: Plinabulin Has Been Successfully Evaluated with Docetaxel in a Phase 3 Study
Plinabulin Has Been Successfully Evaluated with Docetaxel in a Phase 3 Study with Advanced and Metastatic, Pre-treated NSCLC EGFR Wild Type Patients Docetaxel + Plinabulin vs. Docetaxel + Placebo in Patients with EGFR Wild-Type NSCLC Study Plan Primary endpoint Secondary endpoints • Global, randomiz
Slide 19: Balanced Baseline Characteristics
Balanced Baseline Characteristics Docetaxel + Placebo (n=281) Docetaxel + Plinabulin (n=278) Median age, y (range) 60 (25, 85) 61 (37, 82) Sex, n (%) Male 207 (73.7) 199 (71.6) Female 74 (26.3) 79 (28.4) Tumor histology, n (%) Non-squamous 178 (63.3) 154 (55.4) Squamous 100 (35.6) 120 (43.2) Missing
Slide 20: Plinabulin + Docetaxel Met its Primary Endpoint (OS)
Plinabulin + Docetaxel Met its Primary Endpoint (OS) and Showed Significant Improvement in Long-term OS Rate Docetaxel + Docetaxel + placebo Plinabulin Survival Probability (%) OS HR=0.82 mOS benefit 1.1 M Log rank p=0.0399 Log-rank p=0.0399 Months Subjects at Risk Docetaxel (75mg/m2) + placebo 281
Slide 21: Plinabulin + Docetaxel Significantly Improved PFS and ORR
Plinabulin + Docetaxel Significantly Improved PFS and ORR PFS ORR ORR (CR+PR)a, n (%) 16 DP: 14% 14 12 10 D: 9% 8 6 4 2 0 Docetaxel + Placebo Docetaxel + Plinabulin ITT N Median PFS Month HR Log rank (95% CI) P value P value = 0.0404 Docetaxel (D) 281 2.8 (2.76, 2.93) Plinabulin + 278 3.3 (2.89, 3.8
Slide 22: Plinabulin Increases Cycles of Treatment and Improved OS Benefit
Plinabulin Increases Cycles of Treatment and Improved OS Benefit with More Cycles of Treatment OS K-M Graph for treatment cycles ≥4 cycles Consistently improved median OS observed Docetaxel + plinabulin Docetaxel + placebo Censored with more treatment cycles 100 80 Survival Probability (%) 60 40 20
Slide 23: Plinabulin Significantly Reduce Grade Neutropenia with less use of G-CSF
Plinabulin Significantly Reduce Grade 4 Neutropenia (>80% reduction) with less use of G-CSF Use of plinabulin significantly reduced Grade 4 neutropenia Less Use of G-CSF use in each Grade 4 neutropenia, All Cycles Day 8 treatment cycle for Plinabulin Arm 50% Docetaxel + Docetaxel + P<0.0001 Treatmen
Slide 24: Consistent OS Benefit in 24-month follow up; Non-squamous OS HR=0.72
Consistent OS Benefit in 24-month follow up after Database Lock; Non-squamous OS HR=0.72 ITT Non-squamous ITT N Median OS (95% CI) HR Log rank Non-squamous N Median OS (95% CI) HR Log rank P value P value Docetaxel 281 9.3 (8.35, 10.65) Docetaxel 178 8.81 (7.73, 10.65) Plinabulin + 278 10.8 (9.37, 1
Slide 25: DUBLIN-3: Treatment Related Adverse Events
DUBLIN-3: Treatment Related Adverse Events Docetaxel + Placebo Docetaxel + Plinabulin N=278 N=274 n (%) n (%) TEAE All grades Grade 3 Grade 4 All grades Grade 3 Grade 4 Any 276 (99.3) 85 (30.6) 119 (42.8) 273 (99.6) 141 (51.5) 52 (19.0) Hematological Anemia 121 (43.5) 13 (4.7) 0 137 (50.0) 15 (5.5)
Slide 26: Plinabulin Successfully Improved Overall Survival Relative to SOC in 2L/3L NSCLC
Plinabulin Successfully Improved Overall Survival Relative to SOC in 2L/3L NSCLC, an Achievement that has Eluded Other Novel Approaches The addition of plinabulin as a single agent added to 2L/3L NSCLC (EGFR wt) standard-of-care docetaxel led to improved overall survival and enhanced safety Efficacy
Slide 27: Phase 2 Study of Pembrolizumab plus Plinabulin and Docetaxel in Metastatic NSCLC
A Phase 2 Study of Pembrolizumab (Pemb) plus Plinabulin (Plin) and Docetaxel (Doc) in Metastatic NSCLC Patients (pts) Who Failed First-Line Immune Checkpoint Inhibitor: Initial Efficacy and Safety Results ESMO 2024, SITC 2024 presentation 27
Slide 28: Limited Options for 2L/3L NSCLC Patients Who Failed Prior PD-1/L1 Inhibitor
Limited Options for 2L/3L NSCLC Patients Who Failed Prior PD-1/L1 Inhibitor Historical Comparison Data • Docetaxel remains the standard of care for patients with 2L/3L NSCLC without targetable alterations who progress on immune checkpoint inhibitors (ICI) with and without standard chemotherapy. ✓ Se
Slide 29: Merck IIT Phase II 303 Study: 2L/3L NSCLC, Progressed on PD-1/L1
Merck IIT Phase II 303 Study: 2L/3L NSCLC, Progressed on PD-1/L1 Single Site (Peking Union Hospital) in China, Single Arm N=47 Regimen Endpoints • Metastatic NSCLC • Progressed from PD-1/L1 • Keytruda 200mg D1 Q3W • Primary： monotherapy or in comb with (up to 35 cycles) -ORR (RECIST 1.1) platinum do
Slide 30: Efficacy data (cut-off date on 29-Aug-2024) – 2024 SITC Presentation
Efficacy data (cut-off date on 29-Aug-2024) – 2024 SITC Presentation Updated Analysis: 30 patients (ITT) (Proportion of patients who had previously received Keytruda: 100%) median follow-up time: 11.5 month (m) Histology Best Change (%) in Target Lesions Sum of Diameters (SOD) and PFS Squamous 43% N
Slide 31: Duration of Response
Duration of Response Swimmer Plot of Tumor Response (28 patients, Evaluable Population) 31
Slide 32: Safety Summary
Safety Summary Treatment-related adverse events (CTCAE 5.0 ≥ Grade 3) 32
Slide 33: Study Summary
303 Study Summary • Pemb plus Plin and Doc in patients with metastatic NSCLC who experienced disease progression after clinical benefit with ICI was associated with double PFS and DCR compared with historical controls of standard of care docetaxel (median PFS was ~3.7 months with docetaxel in the TR
Slide 34: Encouraging RT+PD-1+Plinabulin Clinical Data Demonstrates Plinabulin's DC Maturation MOA
Encouraging RT+PD-1+Plinabulin Clinical Data Demonstrates Plinabulin’s Dendritic Cell Maturation MOA in Responding Patients Presentation at SITC 2023 RT: Radiation therapy 34
Slide 35: Phase 1b Study to Evaluate Safety of Adding Plinabulin + RT/IO
2020-0296: Phase 1b Study to Evaluate Safety of Adding Plinabulin + RT/IO in IO Relapsed/Refractory Solid Tumors * * RT = 24 Gy/3 fx; 50 Gy/4 fx; 20 Gy/5 fx • Primary endpoint: Safety and ORR/DCR 35
Slide 36: Clinical PoC in Efficacy: Plinabulin Triple Combo Produces Meaningful Responses
Clinical PoC in Efficacy: Plinabulin Triple Combo Produces Clinically Meaningful Responses in the Non-Irradiated Tumor Across Multiple Cancers in CINR Topline Preliminary Data: presented at SITC 2023: Systemic abscopal effect seen comparing baseline and C3D1 Plinabulin triple combination led to >50%
Slide 37: Plinabulin: Transforming Oncology with Novel Mechanisms for Patient Benefits
Plinabulin: Transforming Oncology with Novel Mechanisms for Patient Benefits Unmet Medical needs and Strong global patent MOA in CINR Clinical Success Market Potential protection A first-in-class tubulin Successfully demonstrated Clinically enhanced the anti- BeyondSpring is a global modulator that
Slide 38: SEED Therapeutics: Target Protein Degradation (TPD 2.0) Company
SEED Therapeutics: Target Protein Degradation (TPD 2.0) Company TPD Targets 80% of Disease-Causing Proteins That are Currently Undruggable 38
Slide 39: Significant and Speedy Value Creation at SEED Therapeutics
Significant and Speedy Value Creation at SEED Therapeutics • SEED Uses Unique Target Protein Degradation (TPD) Technology for Novel Drug Discovery; • TPD Platform Has the Potential to Address 80% of Disease-Causing Proteins That are Undruggable 2024: High Value Drug Candidates, Achieved Lilly Invest
Slide 40: SEED Differentiation
SEED Differentiation Scalable Business TPD has potential to target 80% of undruggable disease-causing Model proteins. > 600 E3 ligases to be used for multiple disease areas. Target-Centric Identify the right E3 for POI to increase the success rate in drug Differentiation discovery: Platforms using Q
Slide 41: World Class Leadership Team and Exceptional Insights in TPD Drug Development
World Class Leadership Team and Exceptional Insights in TPD Drug Development Lan Huang, PhD + * Avram Hershko MD, PhD+ Ning Zheng, PhD+ Michele Pagano, MD + (Chairman & CEO) “Godfather” of TPD; Howard Hughes Professor, University of Howard Hughes Professor, NYU E3 structural expert; Serial biotech 2
Slide 42: TPD Development History and Recent Renaissance
TPD Development History and Recent Renaissance TPD Process SEED Co-Founders played pivotal roles in the advancement of TPD field • 1996: Dr. Michele Pagano discovered cell cycle regulation by TPD, including E3 ligases; published in Science • 1999: Dr. Lan Huang solved the 1st of two E3 structures (H
Slide 43: Controlled Protein Degradation: Reprogramming Ubiquitin Ligases with Molecular Glues
Controlled Protein Degradation: Reprogramming Ubiquitin Ligases with Molecular Glues to Target Un-ligandable Proteins Ubiquitin Ligase Target Protein (UBL) LIMITATIONS: ADVANTAGES: × Bi-functional molecule ✓ Involves a single non-chimeric small molecule × >500 Da (may limit cell availability) ✓ Smal
Slide 44: Nature Biotechnology Review on The Glue Degraders
“Nature Biotechnology” Review on “The Glue Degraders” (3/6/2024) SEED was prominently featured in “Nature Biotechnology” Review. Garber, Nature Biotechnology (2024) 44
Slide 45: Nature Reviews Drug Discovery Review on Protein Degraders
“Nature Reviews Drug Discovery” Review on “Protein Degraders Push into Novel Target Space” (10/14/2024) SEED was prominently featured in “Nature Reviews Drug Discovery”. Mullard, Nature Reviews Drug Discovery (2024) 45
Slide 46: Highly Experienced in-House R&D Team
Highly Experienced in-House R&D Team Highly Experienced Internal R&D Team • >100 years combined small molecule hit-to-lead and lead optimization work • >60 years Medicinal Chemistry and SBDD work • >60 years DMPK work • >60 years nonclinical development/safety work • >40 INDs filed • >12 NDAs achiev
Slide 47: Multi-Dimensional and Proprietary Platform for E3 Selection
Multi-Dimensional and Proprietary Platform for E3 Selection Quasi-Interface Analyses LumID: identify the right E3 near POI Basal Affinity Validation in live cell B B E3 B Target Protein Target Quasi Degron Protein Target B 1 Weakened Binding L E3 C A I L A I E3 A E3 E3 Molecular Glue Proteomics B B
Slide 48: Productive Development History
Productive Development History Global Pharma Partnership Milestones Mar. 2024: Received 3rd milestone payment by Lilly Jun. 2022: Received $5M equity investment by Lilly upon achieving 1st milestone; $3M equity investment by Aug. 2024: Received $24M Nov. 2020: Received $10M upfront and $5M equity BY
Slide 49: Diversified and Fast Progressing Pipeline
Diversified and Fast Progressing Pipeline Target Molecular IND Indication Target Protein E3 Ligase ID Lead ID IND Filing Selection Glue HTS Candidate FHD: RBM39 2H 2025 KRAS-G12D Oncology Target Beta FEN1 Target Alpha Tau In Vivo Activity Neurodegeneration Plan: 1H 2025 Target Delta Immunology Targe
Slide 50: RBM39 Degrader: Received FDA Orphan Designation, Expected IND in 2025
RBM39 Degrader: Received FDA Orphan Designation, Expected IND in 2025 Program Summary • POI: RNA splicing factor RMB39; E3: DCAF15; MOA: RMB39 degrader MG • Target indications: Biomarker selected colon cancer, prostate cancer, neuroblastoma, and others • Development stage: IND candidate; FHD in 2H 2
Slide 51: TPD: a High Value and Novel Therapeutic Modality
TPD: a High Value and Novel Therapeutic Modality All top 20 global pharma have TPD programs internally and / or through collaboration Allosteric effect based Covalent binder • Not MG selective Target-Centric • Discovery stage TPD assets has been commanding $35 - $60 libraries • Lack of evidence for
Slide 52: Investment Highlights
Investment Highlights Plinabulin: Safety & Lead Asset Plinabulin: >700 cancer patients treated with good Efficacy tolerability; Positive Phase 3 data in 2/3L NSCLC, EGFR wild type Plinabulin: Dual Benefit in anti-cancer and prevention of CIN; Potential Plinabulin Potential in re-sensitizing in PD-1/
Slide 53: www.beyondspringpharma.com
www.beyondspringpharma.com 53