Slide 1: November 2024 | NASDAQ: BYSI
November 2024 | 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 Overall Survival Benefit: Anti-cancer Efficacy 1. durable anti-cancer benefit in doubling 2-year, 3-year OS rate 2. enables more chemo doses by re
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: Plinabulin: First-in-class Late-Stage Clinical Asset for Cancer Treatment
Plinabulin: First-in-class Late-Stage Clinical Asset for Cancer Treatment 5
Slide 6: First-in-class Asset: Plinabulin
First-in-class Asset: Plinabulin • Positive Phase 3 study in 2L/3L NSCLC, successfully demonstrated significant Advanced Clinical OS benefit, doubling 2-year, 3-year OS rate – proving plinabulin’s clinical Stage Agent utility • Promising efficacy data in combination with PD-(L)1 and radiation, in IO
Slide 7: Plinabulin Unique Tubulin Binder Liberates GEF-H1 Leading to DC Maturation
As a Unique Tubulin Binder, Plinabulin Effectively Liberates GEF-H1 from Microtubules Leading to DC Maturation, M1-polarization and T-cell Activation Plinabulin is a unique tubulin binder1 Plinabulin2 Plinabulin (NPI-2358) Depolymerization of microtubules Plinabulin’s tubulin binding site is distinc
Slide 8: Plinabulin's Immunomodulation and Neutropenia-Mitigating Activities Position It as Valuable Partner
Plinabulin’s Immunomodulation and Neutropenia-Mitigating Activities Position It as a Valuable Partner for Immuno-Chemotherapy Combination Regimens These aspects result in an optimal scenario of added efficacy with potentially reduced toxicity. Dendritic Cells M1-like Macrophages Improves Safety* Pli
Slide 9: 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) • The Lancet Respiratory Medicine (Sept 9, 2024) • BeyondSpring Delivers Oral Presentation at ISLAC 2024 World (globenewswire.com) • BeyondSpring Presents Final Data Analysis of DUBLIN-3 (globenewswire.com) 9
Slide 10: 2L/3L NSCLC 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 Attempts to address treatment needs have are limited been challenging • Docetaxel-based therapies are the mainstay therapy in 2L/3L Since Nivolumab’s approval 9 years ago, no
Slide 11: Plinabulin Evaluated with Docetaxel in a Phase 3 Study in NSCLC
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 12: 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 13: Plinabulin + Docetaxel Met Primary Endpoint (OS) with Long-term OS Rate Improvement
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 14: 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 15: 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 16: Plinabulin Significantly Reduces Grade 4 Neutropenia with Less G-CSF Use
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 17: 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 18: 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 19: 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 20: Encouraging RT+PD-1+Plinabulin Clinical Data Demonstrates DC Maturation MOA
Encouraging RT+PD-1+Plinabulin Clinical Data Demonstrates Plinabulin’s Dendritic Cell Maturation MOA in Responding Patients RT: Radiation therapy 20
Slide 21: Plinabulin Enhances the Cancer Immunity Cycle with Radiation and Anti-PD1
Plinabulin Enhances the Cancer Immunity Cycle When Used with Radiation and Anti-PD1 ② Plinabulin 2 Improved antigen presentation ③ Checkpoint Inhibitors Stimulate maturation of dendritic cells to increase antigen presentation. 3 Anti-tumor T cell activation Optimize T cell response 1 ① Radiation/Che
Slide 22: Plinabulin Evaluated in Multiple Immunotherapy Combination Trials
Plinabulin is Being Evaluated in Multiple Immunotherapy Combination Trials in Collaboration with Major Pharmaceutical Companies Indication/Target Program Preclinical Phase 1 Phase 2 Phase 3 Trial Name / Collaborator ES-SCLC Plinabulin + Pembrolizumab Study 302 (1st line) + Etoposide / Platinum Inves
Slide 23: RT+anti-PD1+Plinabulin Triple Combination POC in Animals
RT+anti-PD1+Plinabulin Triple Combination POC in Animals Provides Evidence of Plinabulin’s Immunomodulatory activity 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 maturation T cell doubles in triple
Slide 24: Clinical PoC in Efficacy: Triple Combo Responses in Non-Irradiated Tumor
Clinical PoC in Efficacy: Plinabulin Triple Combo Produces Clinically Meaningful Responses in the Non-Irradiated Tumor Across Multiple Cancers after IO-failure Topline Preliminary Data: presented at SITC 2023: Systemic abscopal effect seen comparing baseline and C3D1 Plinabulin triple combination le
Slide 25: Clinical PoC in MOA: Early Immune Activation Evidenced by DC Maturation
Clinical PoC in MOA: Plinabulin-Responding Patients Show Early Immune Activation Evidenced by DC Maturation and Proinflammatory Monocytes in the Peripheral Blood In different cancers, DC maturation and anti-tumor inflammatory macrophages were observed in plinabulin-responding patients Proinflammator
Slide 26: 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 11/8/2024 presentation 26
Slide 27: 2L/3L NSCLC Patients Failed Prior PD-1/PD-L1
2L/3L NSCLC Patients Failed Prior PD-1/PD-L1 (no Driver Mutation) Historical 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. • In the recent TROPION L
Slide 28: 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 29: Efficacy Data – 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 30: Duration of Response
Duration of Response Swimmer Plot of Tumor Response (28 patients, Evaluable Population) 30
Slide 31: Plinabulin as Potential Add-on Therapy to Current I/O Regimens
Plinabulin as Potential Add-on Therapy to Current I/O Regimens to Address Severe Unmet Medical Needs PD-1/PD-L1 Inhibitors Potential to greatly expand the - >$40B global annual sales addressable market Current Severe Unmet Medical Needs Plinabulin Clinical Development 2L/3L: PD-1/PD-L1 relapsed/refr
Slide 32: Plinabulin's DC Maturation MoA, Clinical Activity and Patent Protection Favorable for Partnerships
Plinabulin’s DC Maturation MoA, Proven Clinical Activity, and Strong Global Patent Protection are Highly Favorable for Partnerships with Immunotherapy Agents…and Beyond Lead Asset Plinabulin Proven clinical efficacy and Enhances the Strong global patent displays dual IO MOAs safety Cancer-Immunity c
Slide 33: 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 33
Slide 34: Significant and Speedy Value Creation at SEED Therapeutics
Significant and Speedy Value Creation at SEED Therapeutics High Value Drug Candidates, Partnership R&D Infrastructure, Milestones and Cash Flow Organization and Pipeline (2023) Target Molecular IND Indication Target Protein E3 Ligase ID Lead ID IND Filing Selection Glue HTS Candidate RBM39 Mid- 2025
Slide 35: 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 36: TPD Addresses 80% of Disease-Causing Proteins That Were Undruggable
Targeted Protein Degradation (TPD) Addresses 80% of Disease- Causing Proteins That Were Undruggable TPD for Undruggable Proteins Druggable Proteins Sriram et al., Molecular Pharmacology, 2018 36
Slide 37: TPD Development History and Recent Renaissance
TPD Development History and Recent Renaissance TPD Cellular Process SEED Co-founders played pivotal roles in the advancement of TPD field • 1996: Dr. Michele Pagano (SEED co-founder) discovered cell cycle regulation by TPD, including E3 ligases; published in Science Molecular Glue creates a cryptic
Slide 38: 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 39: Experienced In-House R&D Team with IND and NDA Track Record
Experienced in-House R&D Team with 40 IND and 12 NDA Track Record 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
Slide 40: Productive Development History
Productive Development History SEED Internal Program Milestones Translation of SEED Platforms into Drug Development of SEED’s unique TPD platforms and filed Infrastructure and Organization Pipeline of 9 disclosed programs in patents Building various disease areas • Multi-dimensional platforms to sel
Slide 41: SEED's Differentiation: Multi-dimensional Platforms for E3 Selection
SEED’s Differentiation: Multi-dimensional Platforms for E3 Selection Knowledge-based Direct Binding Validation LumID: Identify the right E3 in the Quasi Degron Approach “living cell” near protein of interest B B E3 B Target Neo Target Neo Target 1 Quasi Degron B Weakened Binding I L I L E3 C A A E3
Slide 42: Nature Biotechnology Review on The Glue Degraders
“Nature Biotechnology” Review on “The Glue Degraders” (Mar. 2024) SEED was prominently featured in “Nature Biotechnology” Review. Garber, Nature Biotechnology (2024) 42
Slide 43: Diversified and Fast Progressing Proprietary SEED Pipeline
Diversified and Fast Progressing Proprietary SEED Pipeline Target Molecular IND Indication Target Protein E3 Ligase ID Lead ID IND Filing Selection Glue HTS Candidate RBM39 Mid- 2025 FHD KRAS-G12D Oncology Target Beta FEN1 Target Alpha Neurodegeneration Tau Target Delta Immunology Target Gamma Antiv
Slide 44: Our RBM39 Degrader Class: Potentially Best-in-Class and First-to-Market
Our RBM39 Degrader Class: Potentially Best-in-Class and First-to-Market 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; Mid-2025
Slide 45: 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 46: Investment Highlights
Investment Highlights Plinabulin: Safety & Lead Asset Plinabulin: >700 cancer patients treated with good Efficacy tolerability; Positive Phase 3 data in 2 indications Plinabulin: Dual Benefit in anti-cancer and prevention of CIN; Potential Plinabulin Potential in re-sensitizing in PD-1/PD-L1 progres
Slide 47: www.beyondspringpharma.com
www.beyondspringpharma.com 47