Slide 1: September 2024 | NASDAQ: BYSI
September 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 NSCLC Plinabulin + Docetaxel Study 103 (DUBLIN-3) (2nd/3rd line) Late stage Plinabulin + Studies 105 & 106 CIN Prevention Pegfilgrastim (PROTECTIVE-1 & PROTECTIVE-2) SCLC Plinabulin + Nivolu
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 is a Differentiated First-in-Class Tubulin Binder
Plinabulin is a Differentiated First-in-Class Tubulin Binder with a Unique Clinical Activity and Favorable Safety Profile Plinabulin is a reversible tubulin binder and does not change tubulin dynamics Conventional tubulin binding agents (such as taxanes, vinca alkaloids, and colchicine) alter tubuli
Slide 8: Plinabulin: Induces Innate and Adaptive Immunity
Plinabulin: Induces Innate and Adaptive Immunity 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 deleted DC cells2 P
Slide 9: Plinabulin's Immunomodulation and Neutropenia-Mitigating Activities
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 10: 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) Publication on The Lancet Respiratory Medicine Han B., Feinstein T., Shi Y. et al. Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-bas
Slide 11: The EGFR-wild Type 2L/3L NSCLC Have Been a Historically Difficult Development Space
The EGFR-wild Type 2L/3L NSCLC Have Been a Historically Difficult Development Space Treatment options in Attempts to address treatment 2L/3L NSCLC are limited needs have been challenging Docetaxel-based therapies are the mainstay therapy in 2L/3L Since Nivolumab’s approval 8 years ago, NSCLC (EGFR w
Slide 12: 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, Pre-treated NSCLC Patients Docetaxel + Plinabulin vs. Docetaxel + Placebo in Patients with EGFR Wild-Type NSCLC Study Plan Primary endpoint Secondary endpoints • Global, randomized, single-blinded (patients •
Slide 13: 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 14: 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 …allowing more patients to remain on Docetaxel + plinabulin Censored docetaxel for a longer duration 100 Docetaxel + placebo % Docetaxel exposure >12 cycles 80 S
Slide 15: Plinabulin Reduces >80% of Grade Neutropenia of Docetaxel
Plinabulin Reduces >80% of Grade 4 Neutropenia of Docetaxel Use of plinabulin significantly reduced Grade 4 neutropenia Grade 4 neutropenia, All Cycles Day 8 50% P<0.0001 Percentage of Patients 40% 33.58% 30% 20% 10% 5.13% 0% Docetaxel + Docetaxel + Placebo Plinabulin 30 mg/m2 Similar results were o
Slide 16: 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 standard-of- care led to improved overall survival and enhanced safety Efficacy Safety and tolerab
Slide 17: Encouraging RT+PD-1+Plinabulin Clinical Data Demonstrates Plinabulin's Partnering Potential
Encouraging RT+PD-1+Plinabulin Clinical Data Demonstrates Plinabulin’s Partnering Potential with IO Agents RT: Radiation therapy 17
Slide 18: Plinabulin Enhances the Cancer Immunity Cycle When Used 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 19: Plinabulin is Being 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 20: 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 21: Clinical PoC in MOA: Plinabulin-Responding Patients Show Early Immune Activation
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 22: A 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 European Society for Medical Oncology (ESMO) Congress 2024 Xu, Y. et al. 1330P Phase II study o
Slide 23: Merck IIT Phase II Study (KeyPelms-004): 2L/3L NSCLC
Merck IIT Phase II 303 Study (KeyPelms-004): 2L/3L NSCLC, PD-1/L1 relapsed – Single Site, Single Arm N=47 Regimen Endpoints • Metastatic NSCLC • Progressed from PD-1/L1 monotherapy or in comb • Keytruda 200mg D1 Q3W • Primary： with platinum doublet (up to 35 cycles) -ORR (RECIST 1.1) • 1L PFS > 6 mo
Slide 24: Efficacy data (cut-off date on 29-Apr-2024)
Efficacy data (cut-off date on 29-Apr-2024) First stage Analysis: 19 patients (Proportion of patients who had previously received Pembro: 73.7%) median follow-up time: 12.4 month Best Change (%) in Target Lesions Sum of Diameters (SOD) and PFS 24
Slide 25: 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 26: Plinabulin's DC Maturation MoA, Proven Clinical Activity, and Strong Global Patent Protection
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 27: 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 27
Slide 28: 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 (2022) Target Molecular IND Indication Target Protein E3 Ligase ID Lead ID IND Filing Selection Glue HTS Candidate RBM39 Mid- 2025
Slide 29: 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 30: Targeted Protein Degradation (TPD) Addresses 80% of Disease-Causing Proteins That Are Undruggable
Targeted Protein Degradation (TPD) Addresses 80% of Disease- Causing Proteins That Are Undruggable TPD for Undruggable Proteins Druggable Proteins Sriram et al., Molecular Pharmacology, 2018 30
Slide 31: TPD Development History and Recent Renaissance
TPD Development History and Recent Renaissance SEED Co-founders played pivotal roles in the TPD Process advancement of TPD field • 1996: Dr. Michele Pagano (SEED co-founder) discovered cell cycle regulation by TPD, including E3 ligases; published in Science • 1999: Dr. Lan Huang (SEED co-founder and
Slide 32: 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 33: 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 34: 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 35: 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 36: "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) 36
Slide 37: 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 38: 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 39: 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 40: 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 41: www.beyondspringpharma.com
www.beyondspringpharma.com 41