Beone Medicines Ltd. Class A · SSE:688235
Beone Medicines Ltd. Class A — BeiGene — Investor Day (July 2020)
67 slides from Beone Medicines Ltd. Class A's investor day presentation, Jul 10, 2020
Slide 1: BeiGene Early Development Pipeline and Research
Exhibit 99.1 BeiGene Early Development Pipeline and Research Thursday, July 9, 2020 – 9:00 a.m. ET
Slide 2: Today's Participants
Today’s Participants Xiaodong Wang, Ph.D. John V. Oyler Lai Wang, Ph.D. Eric Hedrick, M.D. Chairman of Scientific Advisory Chairman, Co-Founder, & CEO SVP, Head of Global Research Chief Advisor Board & Co-Founder & APAC Clinical Development Jane Huang, M.D. Yong (Ben) Ben, M.D. Howard Liang, Ph.D. C
Slide 3: Agenda
Agenda Howard Liang, Ph.D. CFO and Chief Strategy Officer
Slide 4: Disclosures
• Certain statements contained in this presentation and in the accompanying oral presentation, other than statements of fact that are independently verifiable at the date hereof, may constitute forward-looking Disclosures statements. Examples of such forward-looking statements include statements reg
Slide 5: Agenda
Agenda • Introduction – Howard Liang • Opening Remarks – Xiaodong Wang BeiGene’s research foundation • BeiGene’s Drug Discovery Engine – Video Presentation People, capabilities, and facilities • Research and Internally Developed Assets – Lai Wang TIGIT, Bcl-2, OX40, and HPK1 • In-Licensed Programs –
Slide 6: Opening Remarks
Opening Remarks Xiaodong Wang, Ph.D. Chairman of Scientific Advisory Board, Co-Founder and Member of Board of Directors
Slide 7: Founded with the Goal of the Best Medicine for the Most People
Founded with the Goal of the Best Medicine for the Most People The founding of a science-based company 10 years ago in China • Why in China? Our philosophy: BeiGene believes the path to the best medicine is following the science • Believe in a core research principle to follow the science: evidence
Slide 8: BeiGene's Drug Discovery Engine Video Presentation
BeiGene’s Drug Discovery Engine Video Presentation
Slide 9: The Discovery Engine
The Discovery Engine Lai Wang, Ph.D. SVP, Head of Global Research and APAC Clinical Development
Slide 10: Executive Summary
Executive Summary BeiGene has built an exceptional research organization with broad capabilities & scope • Strong organization built over last decade and attracted outstanding talent • Broad capabilities exist in this team to attack cancer through many modalities and targets This team has shown prov
Slide 11: The Discovery Engine
The Discovery Engine • Research Organization, Capabilities • Proven Internal Research Track Record • Robust Promising Pipeline 11
Slide 12: Integrated Research Capabilities Offer Opportunities to Address Wide Range of Biological Problems
Integrated Research Capabilities Offer Opportunities to Address Wide Range of Biological Problems • Comprehensive small molecule and biologics discovery engine • Efficient portfolio management • Striving for seamless transition to manufacturing and clinical development 12
Slide 13: Full Suite of Tools Applied Across Oncology and Beyond
Full Suite of Tools Applied Across Oncology and Beyond • Moving beyond oncology to areas such as I/I • Cutting-edge tools such as PROTAC, bispecific Ab, and ADC • Pursuing 10+ potentially best-in- class and first-in-class projects with the plan to double that in one year ADC; Antibody Drug Conjugate
Slide 14: Expansion of BeiGene Research
Expansion of BeiGene Research 2011–2018 TODAY PLANNED IN ONE YEAR Beijing Research Center Beijing Research Center Beijing Research Center ST ND (ONLY 1 AND 2 FLOOR) Shanghai Research Center • Team size <200 • Team size 350+ • 6-8 preclinical programs • ~12 preclinical programs • Team size 650+ • Cap
Slide 15: The Discovery Engine
The Discovery Engine • Research Organization, Capabilities • Proven Internal Research Track Record • Robust Promising Pipeline 15
Slide 16: Proven Internal Research Track Record
Proven Internal Research Track Record Two approved products, with a third at filing stage • BRUKINSA (zanubrutinib) approved in US and China First China-discovered compound to be approved by the FDA and granted Breakthrough Therapy Designation Highly selective, complete and sustained target inhi
Slide 17: The Discovery Engine
The Discovery Engine • Research Organization, Capabilities • Proven Internal Research Track Record • Robust Promising Pipeline 17
Slide 18: Internal Capabilities and Collaborations Create Robust Pipeline
Internal Capabilities and Collaborations Create Robust Pipeline 25+ assets, 8 with global rights DOSE ESC. DOSE EXPANSION PIVOTAL COMPOUND (TARGET) / PROGRAM COMMERCIAL RIGHTS PARTNER PH1a PH1b PH2* PH2** PH3 BGB-A1217 (TIGIT) + tislelizumab Solid tumors Global BGB-A445 (OX40) + tislelizumab Solid t
Slide 19: Cancer Immunotherapy Targets and Combinations
Small Molecule Cancer Immunotherapy Biologics Lenalidomide Sitravatinib Sitravatinib (TAM) (VEGFR) MDSC PD-1/L1 Sitravatinib OX-40 CAB-CTLA4 TIM-3 OX40 TIGIT FAP-4-1BB TIGIT Treg Cytotoxic T Cell TIM-3 TIGIT OX40 TIM-3 Dendritic Cell Natural Killer Cell Source: Modified from Daniel S. Chen, Immunity
Slide 20: Tumor-Targeted Therapy Combinations
Small Molecule Tumor-Targeted Therapy Biologics EGFRvIII-CD3 (GBM) PARPi (GBM) BTKi (NHL) Revlimid (NHL) Blincyto (NHL) CD19-CD3 (NHL) KrasG12Ci (NSCLC) PARPi (BC) DLL3-CD3 (SCLC) HER2 BsAB/BsAB- ADC (HER2+ BC) HER2 BsAB/BsAB-ADC (HER2+ GC, BTC, CRC) MUC17-CD3 (GC) Blincyto (ALL) PARPi (GC) Vidaza (
Slide 21: Robust Promising Pipeline
Robust Promising Pipeline • BGB-A1217 (TIGIT Antibody) • BGB-11417 (Bcl-2 Inhibitor) • BGB-A445 (Non Ligand-Competing OX40 Antibody) • BGB-15025 (HPK1 Inhibitor) 21
Slide 22: Executive Summary: TIGIT Program
Executive Summary: TIGIT Program Encouraging POC data on tiragolumab/atezolizumab (Roche) at ASCO 2020 BGB-A1217 (TIGIT mAb) is one of the three most advanced TIGIT antibodies with full Fc function and RP2D for PD-(L)1 combination • ~4x more potent than tiragolumab in preclinical studies • Competent
Slide 23: TIGIT Ab Activates T/NK Cells by Blocking TIGIT and Ligand Interaction
TIGIT Ab Activates T/NK Cells by Blocking TIGIT and Ligand Interaction • TIGIT shares its ligand PVR (CD155) and PVR-L2 (CD112) with the activating receptor CD226 (DNAM-1) • BGB-A1217 blocks the binding of PVR/PVR-L2 to TIGIT and reactivates T effector cells and NK cells by: Suppressing TIGIT-medi
Slide 24: ASCO Update: Roche's Tiragolumab plus Atezolizumab in 1L PD-L1+ NSCLC
ASCO Update: Roche’s TIGIT (Tiragolumab) plus PD-L1 (Atezolizumab) Combo Demonstrated Promising Activity in 1L PD-L1+ NSCLC Study Design (CITYSCAPE) Results: ITT (TPS≥1%) PD-L1 high (TPS≥50%) PD-L1 low (TPS≥1-49%) N=135 n=58 n=77 Tiragolumab Placebo Tiragolumab Placebo Tiragolumab Placebo +Tecentriq
Slide 25: Fc Effector Function Appears Critical for Anti-Tumor Activity of TIGIT Ab
Fc Effector Function Appears Critical for Anti-Tumor Activity of TIGIT Ab Competent Fc is required for BGB-A1217 in CT26 model Myeloid Cell 2500 2500 V ehicle V ehicle 2. Proinflammatory SEM) SEM) ± ± 3 BGB-A1217 with competent Fc 3 BGB-A1217 with silent Fc FcγR tumor 2000 2000 microenvironment 1500
Slide 26: TIGIT Competitive Landscape
TIGIT Competitive Landscape FORMAT HYPOTHESIS DRUG NAME COMPANY COMBO DOSE STATUS Ph1 initiated in May 2016 Ph2 in cervical cancer planned in Jun 2020 Tiragolumab Roche 600 mg Q3W Ph3 in SCLC initiated in Feb 2020 Ph3 in NSCLC initiated in Mar 2020 Ph1 initiated in Dec 2016 Vibostolimab Merck Not di
Slide 27: BGB-A1217 Program Moving Aggressively Towards Registration Trial
BGB-A1217 Program Moving Aggressively Towards Registration Trial • Four-fold more potent than tiragolumab (Roche)1 • BGB-A1217 Phase 1 combination with tislelizumab ongoing in advanced solid tumors • Generally well-tolerated, no DLT, combination recommended phase 2 dose has been determined • Full ta
Slide 28: Robust Promising Pipeline
Robust Promising Pipeline • BGB-A1217 (TIGIT Antibody) • BGB-11417 (Bcl-2 Inhibitor) • BGB-A445 (Non Ligand-Competing OX40 Antibody) • BGB-15025 (HPK1 Inhibitor) 28
Slide 29: Executive Summary: Bcl-2 Program
Executive Summary: Bcl-2 Program BGB-11417 is a potential best-in-class Bcl-2 inhibitor • Potent Bcl-2 inhibitor, with potential to overcome resistance to venetoclax • Ability to be dosed high if needed, e.g. for solid tumor indications • More selective than venetoclax for Bcl-2 relative to Bcl-xL •
Slide 30: BGB-11417 More Potent and Selective than Venetoclax
BGB-11417 Was More Potent and Selective than Venetoclax in Biochemical and Cellular Assays Potency Improvement BGB-11417 Venetoclax (Fold, BGB-11417/Venetoclax) Bcl-2 WT (Biochemical IC50, nM) 0.035 1.3 37 Bcl-2 G101V (Biochemical IC50, nM) 0.28 34 121 Bcl-2 WT (Cell Proliferation IC50, nM) 0.42 3.4
Slide 31: BGB-11417 More Efficacious than Venetoclax in Xenograft Models
BGB-11417 Was More Efficacious than Venetoclax in Both Wild-Type and Bcl-2-G101V Xenograft Models BGB-11417 is more efficacious in RS4:11 model BGB-11417 is efficacious in RS4:11-G101V model V ehicle V ehicle 3000 BGB-11417 5 mpk p.o. QD 3000 SEM) BGB-11417 5 mpk p.o. QD SEM) BGB-11417 15 mpk p.o. Q
Slide 32: Bcl-2 Inhibitors Demonstrated Activity in Solid Tumors
Bcl-2 Inhibitors Demonstrated Activity in Solid Tumors Breast cancer • Bcl-2 is overexpressed in approximately 80% of primary ER+ breast cancer1, 2. Bcl-2 is often expressed at high levels in poorer-prognosis luminal B tumors, as well as good-prognosis luminal A tumors3. • Combining venetoclax with
Slide 33: Robust Promising Pipeline
Robust Promising Pipeline • BGB-A1217 (TIGIT Antibody) • BGB-11417 (Bcl-2 Inhibitor) • BGB-A445 (Non Ligand-Competing OX40 Antibody) • BGB-15025 (HPK1 Inhibitor) 33
Slide 34: Executive Summary: OX40 Program
Executive Summary: OX40 Program BGB-A445 (OX40 agonist antibody) is differentiated from all other OX40 Abs in the clinic • Does not disrupt OX40-OX40L engagement Retains OX40L signaling on antigen presenting cells Achieves maximal OX40 activation by keeping natural ligand stimulation • Widely ef
Slide 35: BGB-A445 Is a Non-ligand Blocking OX40 Antibody
BGB-A445 Is a Non-ligand Blocking OX40 Antibody, Differentiated from Other Clinical OX40 Antibodies APC APC APC activation OX40L Ligand OX40L blocking Ab e.g. MOXR0916 OX40 OX40 APC T cell APC T cell activation At higher concentration, a ligand blocking At lower concentration, a ligand blocking OX40
Slide 36: BGB-445 Showed Dose-Response While Competitor Showed Hook Effect
BGB-445 Showed Dose-Response, While Competitor’s OX40 Ab Showed Hook Effect in MC38 OX40 Humanized Mice Model Tumor Growth Inhibition (%)1 1 1 EFC-MC38(DC)-1919BGB-A445 ReferenceReference OX40 OX40 Ab 90 80 2000 2500 V eh icle SEM) vehicle SEM) 70 ± ± Reference OX40 Ab 0.4 mpk 3 3 BGB-A445 0.4m pk 2
Slide 37: OX40 Competitive Landscape
OX40 Competitive Landscape DRUG NAME DESCRIPTION COMPANY DISEASE STATUS IgG1 OX40 agonist Ph1 initiated in Aug 2014 MOXR-0916 Roche Solid tumors Block OX40L Development discontinued in 2017 Ph1 initiated in Mar 2016 IgG1 OX40 agonist Ph1b in HNSCC/melanoma initiated in Jul 2018 MEDI-0562 MedImmune/A
Slide 38: OX40 Ab Was More Efficacious than PD-1 in Mouse Models
OX40 Ab Was More Efficacious than PD-1 in Mouse Syngeneic Models CT26WT A20 MC38 (K) H22 3LL TrampC2 EG7 SEM) 2000 SEM) SEM) 2500 4000 ± 600 SEM) ± SEM) ± 2500 3 3000 ± 2000 3 3 ± 3 SEM) SEM) 3 3 3 2000 1500 2000 3000 1500 *** Responded to 2000 400 *** ** 1500 1500 ** **** * * 1000 2000 1000 ** * **
Slide 39: OX40 Ab Combination Activity
OX40 Ab Has Shown Combination Activity with PD-1 Ab, PI3Kδ Inhibitor, Sitravatinib, TLR9 Agonist, and Chemo MC38 model EMT6 model CT26 model V ehicle OX40 Ab (10/25 TF) V ehicle SEM) 3000 V ehicle ± OX40 Ab (10/20 TF) 1500 PI3Kδi (1/25 TF) 3000 3 ±SEM) ±SEM) OX40 Ab 3 3 sitravatinib (1/20 TF) PI3Kδi
Slide 40: Ph1 Study Design and Status of BGB-A445
Ph1 Study Design and Current Status of BGB-A445 (OX40 Antibody) Dose Escalation Dose Expansion A445 600 mg A445 600 mg + tislelizumab A445 300 mg A445 300 mg + tislelizumab BGB-A445 ± tislelizumab RP2D 2-4 cohorts of 20-40 pts/cohort A445 150 mg A445 150 mg + tislelizumab A445 60 mg A445 20 mg • Dos
Slide 41: Robust Promising Pipeline
Robust Promising Pipeline • BGB-A1217 (TIGIT Antibody) • BGB-11417 (Bcl-2 Inhibitor) • BGB-A445 (Non Ligand-Competing OX40 Antibody) • BGB-15025 (HPK1 Inhibitor) 41
Slide 42: Executive Summary: HPK1 Program
Executive Summary: HPK1 Program BGB-15025 is a potentially first-in-class HPK1 inhibitor • HPK1 is a key negative feedback regulator of TCR signaling; inhibition of HPK1 enhances T cell activation • Robust combination anti-tumor activity with PD-1 Ab in preclinical animal models1 • Preliminary tox s
Slide 43: HPK1 Negatively Regulates T-cell Receptor Signaling
HPK1 Negatively Regulates T-cell Receptor Signaling Sairy Hernandez et al, Cell Reports 25, 80–94, 2018 Phosphorylation of the adaptor SLP-76 by HPK1 leads to degradation of SLP-76 which is crucial for T-cell activation. Sources: Adopted and modified from Koretzky G. et al Nature Review Immunology 2
Slide 44: Scientific Evidence for Role of HPK1 in T-Cell Activation
Strong Scientific Evidence Supports Critical Role for HPK1 in T-Cell Activation and Anti-Tumor Immunity T-cells with reduced HPK1 catalytic activity show Tumor rejection in GL261 model in HPK1 enhanced activation upon αCD3 treatment kinase dead mice HPK1 wt HPK1 knockout HPK1 kinase dead HPK1 M91A*
Slide 45: BGB-15025 Significant in Vitro and in Vivo PD Effect
BGB-15025 Demonstrated Significant in Vitro and in Vivo PD Effect BGB-15025 increased IL2 production in PBMC Splenic pSLP76 PD (6hr post treatment) 10000 40 ,% 8000 30 * 6000 20 ** 4000 *** IL-2(pg/m l) 10 2000 C D 8+pSLP76+/CD 8+ 0 0 0 1 3 10 30 100 300 1000 3000 Control V e h ic le BGB-15025[nM] B
Slide 46: BGB-15025 Combo Efficacy with PD-1 Antibody
BGB-15025 Showed Significant Combo Efficacy with PD-1 Antibody 3000 3000 Vehicle PD1 Ab 2000 ) 2000 ) 3 3 (m m (m m Tumor- TV<50 TV<100 Group Dosage 1000 1000 free mm3 mm3 Vehicle - 0 0 0 0 0 (n=15) Individual Tumor Volume Individual Individual Tumor Volume Individual 0 5 10 15 20 25 0 5 10 15 20 25
Slide 47: Productive Discovery Engine
Productive Discovery Engine Always science driven, proven record in target selection Full internal capabilities, efficient portfolio management Cutting edge technologies such as PROTAC, ADC, bsAb Robust early pipeline (25+ in clinical stage and 10+ in preclinical), including: • BGB-A1217 (TIGIT): On
Slide 48: In-Licensed Programs
In-Licensed Programs Eric Hedrick, M.D. Chief Advisor
Slide 49: Executive Summary: External Collaborations
Executive Summary External collaborations contribute significantly to our clinical pipeline: • 25+ molecules across 9 collaborations • Complementary with existing internal clinical and research programs • Diversification of therapeutic modalities (e.g. Amgen BiTE platforms) • Expansion of IO tisleli
Slide 50: Internal Capabilities and Collaborations Create Robust Pipeline
Internal Capabilities and Collaborations Create Robust Pipeline 25+ assets, 8 with global rights DOSE ESC. DOSE EXPANSION PIVOTAL COMPOUND (TARGET) / PROGRAM COMMERCIAL RIGHTS PARTNER PH1a PH1b PH2* PH2** PH3 BGB-A1217 (TIGIT) + tislelizumab Solid tumors Global BGB-A445 (OX40) + tislelizumab Solid t
Slide 51: In-Licensed Programs
In-Licensed Programs • Sotorasib* (AMG 510) • Sitravatinib • Zanidatamab (ZW25) (HER-2 Bispecific Antibody) * AMG 510 (proposed INN Sotorasib) 51
Slide 52: Executive Summary – Sotorasib (AMG 510) Program
Executive Summary – Sotorasib* (AMG 510) Program Small molecule covalent KRASG12C inhibitor • Historically difficult drug target; Amgen’s key discovery was a surface groove on KRASG12C exploited to optimize potency and advance into clinic • Estimated incidence of KRASG12C lung cancer in Chinese pati
Slide 53: Sotorasib (AMG 510) in NSCLC
Sotorasib (AMG 510) in NSCLC Phase 1 data from ESMO 2019 TIME TO RESPONSE AND TREATMENT OVER TIME At 960mg RP2D N=13, PR 7 (54%), SD 6 (46), ORR 54%; Data cutoff: July 17, 2019 53
Slide 54: Sotorasib (AMG 510) in CRC
Sotorasib (AMG 510) in CRC Data from ASCO 2020 At 960mg RP2D N=12, PR 1 (8%), SD 10 (83), ORR 8%; Data cutoff: July 17, 2019 54
Slide 55: In-Licensed Programs
In-Licensed Programs • Sotorasib* (AMG 510) • Sitravatinib • Zanidatamab (ZW25) (HER-2 Bispecific Antibody) 55
Slide 56: Executive Summary - Sitravatinib Program
Executive Summary - Sitravatinib Program* Sitravatinib: small molecule multi-kinase inhibitor • In addition to being a potent inhibitor of VEGFR, sitravatinib is also a potent inhibitor of: Axl, Tyro3, and MerTK • These kinases are involved in tumor-associated macrophage activities (polarization and
Slide 57: Sitravatinib/Nivolumab Activity in PD(L)-1 Refractory Tumors
Sitravatinib/Nivolumab Combination Has Significant Clinical Activity in Patients with PD(L)-1 Refractory Tumors Non-squamous NSCLC Confirmed ORR 16% MRTX-500: Overall Survival, PCB Cohort: 1 or 2 Prior Lines of Treatment, N=73, Data as of January 30, 2020 PCB - Prior Clinical benefit (i.e., RECIST d
Slide 58: Sitravatinib/Tislelizumab in Platinum Resistant Ovarian Cancer
Sitravatinib/Tislelizumab Combination Preliminary Antitumor Activity in Platinum Resistant Ovarian Cancer Source: ESMO IO 2019 58
Slide 59: In-Licensed Programs
In-Licensed Programs • Sotorasib* (AMG 510) • Sitravatinib • Zanidatamab (ZW25) (HER-2 Bispecific Antibody) 59
Slide 60: Executive Summary – Zanidatamab (ZW25) Program
Executive Summary – Zanidatamab (ZW25) Program Zanidatamab: bispecific antibody targeting two distinct HER2 epitopes1 • Zanidatamab biparatopic – targets extracellular domain 2: ECD2 (trastuzumab binding domain) and ECD4 (pertuzumab binding domain) • Unique binding geometries of zanidatamab promoted
Slide 61: Collaborations Are a Central Part of Our Comprehensive Pipeline
Collaborations Are a Central Part of Our Comprehensive Pipeline Broad set of ongoing clinical collaborations that significantly augment our internal discovery, ongoing clinical development programs, and commercial products (tislelizumab and zanubrutinib) Many programs planned to go to pivotal/late-s
Slide 62: Concluding Remarks
Concluding Remarks John V. Oyler Chairman, Co-Founder & CEO
Slide 63: Summary: Research and Early Development
Summary: Research and Early Development Internal R&D platform generating robust, sustainable pipeline • Proven: Two approved medicines (and another at the filing stage) with excellent clinical profiles • Cutting Edge: Utilizing cutting edge technologies to address a wide range of biological problems
Slide 64: Recent Accomplishments and Upcoming Milestones
China Recent Accomplishments and Upcoming Milestones Global Past 10 Months (From 4Q19 – YTD) Disclosed Milestones Over Next 18 Months 11 9 Tisle 1L NPC tislelizumab Tisle 1L ESCC 7 pamiparib BRUKINSA Pami 3L 6 25+ R/R MZL gBRCA+ OC BRUKINSA BRUKINSA Tisle 2/3L R/R CLL/SLL Biologics HTH CLL/SLL HCC 5
Slide 65: Future Vision
Future Vision Once in a lifetime period of transformation in our industry, which creates opportunities for smaller players to become leaders BeiGene is one of the best positioned companies for this opportunity On this journey, BeiGene is striving to • Become an oncology and scientific leader • Expan
Slide 66: Q&A
Q&A Participants: • Xiaodong Wang, Ph.D. • Eric Hedrick, M.D. • John V. Oyler • Yong (Ben) Ben, M.D. • Howard Liang, Ph.D. • Jane Huang, M.D. • Lai Wang, Ph.D.
Slide 67: Thank You
Thank You