Beone Medicines Ltd. Class A · SSE:688235
Beone Medicines Ltd. Class A — BeiGene — Investor Presentation (January 2019)
53 slides from Beone Medicines Ltd. Class A's investor presentation, Jan 7, 2019
Slide 1: Corporate Presentation January 6, 2019
Corporate Presentation January 6, 2019
Slide 2: Disclosures
2 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 statements . Examples of such forward - looking statements include those r
Slide 3: Building a Leading Global Innovative Biotech Company From China
Capture opportunities created by regulatory reforms in China and continue to expand our portfolio Realize two large near - term commercial opportunities: BTK globally and PD - 1 in Asia 3 Strengthen and deepen key strategic capabilities including global clinical development and commercial footprint
Slide 4: Evolution of BeiGene
Evolution of BeiGene RESEARCH AND DISCOVERY 2010 - 2012 x Founded by John Oyler and Xiaodong Wang in Beijing x Established commitment to patients , science and quality x Established research capability 4 2013 - 2016 x Established global footprint and clinical capabilities x Advanced four internally
Slide 5: Experienced Management Team
John V. Oyler Founder, CEO, and Chairman Xiaodong Wang, Ph.D. Founder and Chairman SAB Xiaobin Wu, Ph.D. GM of China, President Howard Liang, Ph.D. CFO and Chief Strategy Officer Eric Hedrick, M.D. Chief Advisor Jane Huang, M.D. Chief Medical Officer ， Hematology Ivan Yifei Zhu Co - Commercial Offic
Slide 6: BeiGene Product Portfolio and Pipeline
Internally - Developed 6 GAZYVA ® combo (CD20) monotherapy PROGRAM (TARGET) DOSE EXPANSION PIVOTAL PH1b PH2* PH2** PH3 DOSE ESC. PH1a * Some indications will not require a non - pivotal Ph2 clinical trial prior to beginning pivotal Ph2 or Ph3 clinical trials. **Conf irmatory clinical trials post app
Slide 7: Realizing two large near-term commercial opportunities: BTK and PD-1
Capture significant global market share by demonstrating differentiation Capture large China opportunity with a broad development program WM, CLL, MCL (China), FL Lung, liver, gastric, and esophageal cancers, classical Hodgkin’s lymphoma (China), urothelial cancer (China) ▪ NDAs for R/R MCL and R/R
Slide 8: Zanubrutinib (BGB-3111, BTK) development programs
R/R marginal zone lymphoma (MZL) Relapsed / Refractory (R/R) chronic lymphocytic leukemia / small lymphocytic leukemia (CLL/SLL) (NDA Accepted) 8 China zanubrutinib + GAZYVA ® (BTK + CD20) tislelizumab + zanubrutinib (PD - 1 + BTK) Worldwide Worldwide Worldwide PROGRAM (TARGET) COMMERCIAL RIGHTS DOS
Slide 9: Tislelizumab (BGB-A317, PD-1) development programs
tislelizumab + pamiparib (PD - 1 + PARP) tislelizumab + zanubrutinib (PD - 1 + BTK) Worldwide (Heme Malignancies); Asia ex - Japan (Solid Tumors) Worldwide Worldwide PROGRAM (TARGET) COMMERCIAL RIGHTS 1 DOSE EXPANSION PIVOTAL PH1b PH2* PH2** PH3 DOSE ESC. PH1a tislelizumab ( BGB - A317 , PD - 1) Sol
Slide 10: Robust Pipeline Beyond BTK and PD-1
Solid tumors: tislelizumab + BGB - A333 (PD - L1) Robust Pipeline Beyond BTK and PD - 1 p amiparib PARP Inhibitor ▪ Global gastric Ph3 trial initiated ▪ Two China pivotal trials ongoing in ovarian cancer s itravatinib 1 Multi - Kinase Inhibitor ▪ Combination with tislelizumab initiated ▪ In - licens
Slide 11: Leverage China to Pursue Global Clinical Excellence
Leverage China to Pursue Global Clinical Excellence BeiGene Is Becoming a Leader in China - Global Clinical Development Pursue a true global model for growth by leveraging China • Clinical team of over 700 , with over 50% in China and remainder in US, EU, AU • Largest oncology - focused clinical dev
Slide 12: Developing Strong Manufacturing Capabilities
• Joint venture with Guangzhou Development District • Investment of $300+ million -- mostly from external funding but BeiGene retains majority equity ownership • 100,000 square meter manufacturing site; 24,000 - liter commercial - scale biologics manufacturing facility • First phase of the manufactu
Slide 13: Marketed Product Growth and Commercial Team Expansion
Marketed Product Growth and Commercial Team Expansion 13 Building Oncology - focused Commercial Footprint *REVLIMID ® approved as a combination therapy with dexamethasone; 1. As of December 25, 2018. 2. As of September 30, 2018. NRDL = Nationa l Reimbursement Drug List, PRDL = Provincial Reimburseme
Slide 14: Effectively Operating in China Can Significantly Enhance Global Development
Effectively Operating in China Can Significantly Enhance Global Development ▪ Single biggest time and money sink for drug development is trial enrollment ▪ Adding China significantly accelerates enrollment of global trials – China alone has 4.3 million new cancer patients in 2015, as large as the U.
Slide 15: Established Collaborations Leverage China Capabilities
▪ BeiGene r etains tislelizumab rights in Asia (ex - JP), hematological malignancies, and internal combinations ▪ Obtained Celgene’s commercial operations and license to three marketed products in China ▪ Tislelizumab joint global development program in Asia - prevalent cancers leverages BeiGene’s s
Slide 16: Expanding National Reimbursement, at Reasonable Prices
CONMANA IRESSA FASLODEX TARCEVA AFINITOR HERCEPTIN TYKERB AITAN ZYTIGA VELCADE REVLIMID AVASTIN NEXAVAR MABTHERA VIDAZA SANDOSTATIN - LAR ZYKADIA AIYANG GIOTRIF TASIGNA FUKEWEI INLYTA SUTENT NINLARO TAGRISSO XALKORI VOTRIENT STIVARGA ERBITUX IMBRUVICA ZELBORAF Expanding National Reimbursement, at Re
Slide 17: NRDL Reimbursement Roughly Doubles Reimbursed Market for Oncology
17 NRDL Reimbursement Roughly Doubles Reimbursed Market for Oncology – China Previously Is Already Second Largest Rx Market Globally PwC Report on Global Pharmaceutical Trend, IMS Health data, McKinsey Industry Report Population (millions of people ) 57 57 59 65 66 69 81 81 81 82 96 98 105 105 127 1
Slide 18: China Enables a Model to Succeed in an Evolving Global Environment
18 China Enables a Model to Succeed in an Evolving Global Environment China enables an alternative model, which is no longer reliant on US pricing Dramatic changes to biopharma industry occurring – China increasingly key focal point for future Expand global access to medicines to 3 - 4B people (~3x
Slide 19: 2018 Accomplishments
x MCL China 1 • 84% ORR • 59% CR x WM global Ph1 2 • 82% MRR • 41% VGPR x Pooled safety data from 476 patients 3 • Low rate of A - fib (2%, only 1 Gr3) • Low rate of severe hemorrhage (2%) x China NDAs R/R MCL and R/R CLL/SLL announced acceptance 8/26 and 10/24 x Priority review status granted to ND
Slide 20: 2019 Milestones and Catalysts
2019 Milestones and Catalysts 20 Zanubrutinib (BTK Inhibitor) Timing ▪ Approval in China for MCL and CLL ▪ China pivotal Phase 2 data and NDA filing for WM in China ▪ Phase 3 data of zanubrutinib vs. ibrutinib in WM ▪ NDA filing in the U.S. ▪ Updated data from global Ph.1 in WM and MCL, pivotal data
Slide 21: Strong Cash Position
Strong Cash Position As of (Amounts in thousands of U.S. Dollars) September 30, 2018 (unaudited) December 31, 2017 (audited) Cash, cash equivalents, restricted cash and short - term investments $ 2,101,072 $ 837,516 Accounts receivable 37,372 29,428 Unbilled receivables 4,878 -- Working capital 1,99
Slide 22: Review of Product Candidates
Review of Product Candidates 22
Slide 23: Zanubrutinib overview
23 OVERVIEW ▪ Optimized pharmacologic properties relative to ibrutinib: superior bioavailability and higher selectivity ▪ Development hypothesis: more complete target inhibition, deeper responses, and favorable safety profile CLINICAL DATA ▪ More than 1,500 patients enrolled across trials, including
Slide 24: Zanubrutinib pharmacokinetics versus ibrutinib
0 100 200 300 400 500 600 700 0 6 12 18 24 Time post - dose (hours) 560mg QD 0 100 200 300 400 500 600 700 0 6 12 18 24 Time post - dose (hours) 100mg QD Adapted from Advani et al ., JCO, 2013 ▪ Cmax and AUC of zanubrutinib at 80mg QD appear to be similar to those of ibrutinib at 560mg ▪ Free drug e
Slide 25: Zanubrutinib Efficacy in WM
Overall Response Rate (ORR) Progression Free Survival (PFS) 25 Zanubrutinib Efficacy in WM Favorable Response Depth and Durability *Of 32 efficacy evaluable patients (43%) with hemoglobin <10 g/dL at baseline, the median increased from 8.9 g/dL (range, 6.3 - 9. 8) to 13.4 g/dL (range, 7.7 - 17.0). T
Slide 26: Ibrutinib Efficacy in WM
100 90 80 70 60 50 40 30 20 10 0 No. of Subjects at Risk Month 63 62 59 55 50 50 45 37 24 17 8 0 3 6 9 12 15 18 21 24 27 30 Ibrutinib Efficacy in WM Best Response in WM ibrutinib Enrolled, n 63 Median Time - on - Treatment 19.1 months Response Criteria Modified 3 rd IWWM (IgM only) Median Prior Line
Slide 27: Zanubrutinib Efficacy in CLL/SLL
zanubrutinib TN CLL R/R CLL Total CLL n 16 50 66 Median follow - up (mo) 7.6 14.0 10.5 Best Response ORR CR PR PR - L SD Non - evaluable* 16 (100%) 1 (6%) 13 (81%) 2 (13%) 0 0 46 (92%) 1 (2%) 41 (82%) 4 (8%) 3 (6%) 1 (2%) 62 (94%) 2 (3%) 54 (82%) 6 (9%) 3 (5%) 1 (2%) 27 Zanubrutinib Efficacy in CLL/
Slide 28: Ibrutinib Efficacy in CLL/SLL
Progression Free Survival (Treatment - Naïve) Progression Free Survival (Relapsed / Refractory) Overall Response Rate (Relapsed / Refractory) n 136 Median FU ( mo) 18.4 Best Response ORR CR PR PR - L SD PD 117 (86%) 5 (4%) 107 (79%) 5 (4%) NR NR n 85 Median FU (mo) 20.9 Best Response ORR CR PR PR -
Slide 29: Ibrutinib Discontinuation for Toxicity or Progression in CLL/SLL
Treatment - Naïve (n=80) Relapsed/Refractory (n=536) Total (n=616) Median Follow - Up 14.5 months Total Treatment D/C 19 (24%) 231 (43%) 250 (41%) Toxicity/Tolerability 12 (15%) 117 (22%) 129 (21%) CLL/SLL Progression 3 (4%) 49 (9%) 52 (8%) Transformation (RT or HD) 0 (0%) 10 (2%) 10 (2%) Death Unre
Slide 30: Zanubrutinib Discontinuation in CLL/SLL Is Uncommon
Treatment - Naïve (n=18) Relapsed/Refractory (n=51) Total (n=69) Median Follow - Up 10.3 months Total Treatment D/C 0 (0%) 2 (4%) 2 (3%) Toxicity/Tolerability 0 (0%) 1 (2%) 1 (1%) CLL/SLL Progression 0 (0%) 0 (0%) 0 (0%) Transformation (RT or HD) 0 (0%) 1 (2%) 1 (1%) 30 Zanubrutinib Discontinuation
Slide 31: Zanubrutinib Safety and Tolerability Summary
▪ Very low rates of headache and hypertension (6.7% and 6.3%) ▪ Concomitant use of vitamin K antagonists was allowed in these zanubrutinib trials ▪ Paucity of treatment discontinuation for adverse events Adverse Events of Interest for BTK Inhibitors in Patients Treated with Zanubrutinib *Resulting i
Slide 32: Zanubrutinib Responses Across Multiple B-Cell Malignancies
TN CLL/SLL R/R CLL/SLL R/R CLL/SLL WM MZL MCL MCL FL FL DLBCL Source 14 - ICML 1 14 - ICML 1 Top - line data from China pivotal trial 5 IWWM 2018 2 ASH 2017 3 ASH 2018 3 China Pivotal Data ASH 2018 4 ASH 2017 3 CSCO 2018 5 ASH 2017 3 n 16 50 91 73 9 45 86 17 26 26 Follow - up (med) 7.6 mo 14.0 mo 9.
Slide 33: Zanubrutinib Plus Obinutuzumab Combination in Follicular Lymphoma
▪ Overall response rate and complete responses to date compare favorably to those achieved with respective single - agents and recen tly approved therapies FL zanubrutinib + obinutuzumab zanubrutinib Ibrutinib Obinutuzumab Idelalisib Source ASH 2017 1 ASH 2017 2 ASH 2016 3 JCO 2013 4 NEJM 2014 5 n 2
Slide 34: Zanubrutinib Global Development Program
Phase 2: Monotherapy, R/R Non - GCB DLBCL Phase 1b/2: Zanubrutinib + tislelizumab , PCNSL and RT Zanubrutinib vs. Ibrutinib WM Phase 3 Zanubrutinib vs. BR 1L CLL/SLL Phase 3 Zanubrutinib vs. Ibrutinib R/R CLL/SLL Phase 2 Pivotal Obinutuzumab ± Zanubrutinib R/R FL Phase 2 Pivotal R/R CLL/SLL Phase 2
Slide 35: Ongoing Pivotal Study Design: Zanubrutinib vs Ibrutinib in WM
1L=first - line treatment for CLL/SLL; BID=twice daily, CLL=chronic lymphocytic leukemia, FCR=fludarabine, cyclophosphamide, and r ituximab, ORR=overall response rate, OS=overall survival, PD=progressive disease, PFS=progression - free survival, R=randomization, SLL=small lymphocytic lymphoma, TN=tr
Slide 36: Ongoing Pivotal Study Designs
Ongoing Pivotal Study Designs 36 R 1:1 R/R CLL/SLL ≥ 1 prior treatment (N=400) Arm B Ibrutinib 420mg QD (n = 200) Arm A Zanubrutinib 160mg BID (n = 200) Relapsed/Refractory CLL/SLL (received ≥ 1 prior treatments) • Age • Geographic Region • Refractory Status • Del[17p]/TP53 mutation status Primary E
Slide 37: Tislelizumab overview
37 OVERVIEW ▪ Tislelizumab is a PD - 1 checkpoint inhibitor with distinct molecular structure and an engineered Fc region; believed to minimize potentially negative interactions with other immune cells 1 – Pivotal data in lead indication: 86% ORR (61% CR) in R/R cHL ▪ Broad development in Asia - pre
Slide 38: Tislelizumab's Lack of FcγR Binding
Fc RI - + Nivolumab Pembrolizumab CD8 + T cell CD4 + T cell - Fc RI Macrophage Monocyte MDSC Dendritic cell + Tislelizumab Antibody - Dependent Cellular Phagocytosis Based on FcγR Binding Tislelizumab has minimal FcγRI binding thus abrogating ADCP activity Tislelizumab’s Lack of FcγR Binding Is
Slide 39: Tislelizumab China cHL Pivotal Trial Data
IRC Dataset cHL Enrolled Patients N=70 Median Follow - up 7.85 months Prior Lines, Median (range) 3 (2 - 11) ORR 85.7% CR 61.4% PR 24.3% 39 Source: Song et al., ASH 2018. *Mediastinal mass ratio of 0.33 or size of any single node/nodal mass ≥10 cm in diameter. . Tislelizumab China cHL Pivotal Trial
Slide 40: Summary of Tislelizumab Adverse Events
Event, n (%) N=70 Grade ≥3 TEAE 15 (21.4) Serious TEAE 1 11* (15.7) TEAE leading to treatment discontinuation 4 † (5.7) TEAE leading to death 0 (0.0) Immune - related (ir) TEAEs (by aggregate category) ≥1 irTEAE 24 (34.3) Thyroid disorder 13 (18.6) Pneumonitis 4 (5.7) Skin adverse reactions 4 (5.7)
Slide 41: Tislelizumab Monotherapy Responses Across Tumor Types
Tumor Type Gastric Cancer Esophageal Cancer Head & Neck SCC Ovarian Cancer Hepatocellular Carcinoma Urothelial Cancer NSCLC MSI - H / dMMR Source ESMO - IO 2018 1 ESMO - IO 2018 1 ESMO 2017 2 ESMO 2017 3 ESMO - IO 2018 1 ESMO - IO 2018 4 ESMO - IO 2018 1 CSCO 2018 5 Median Treatment Duration -- -- 1
Slide 42: Tislelizumab Common Adverse Events
Tislelizumab Phase 1 Common AEs in ≥ 10% of Patients System Organ Class Preferred Term Phase 1a Phase 1b Total N=116 n (%) N=335 n (%) N=451 n (%) Patients with at least one TEAE 114 (25.3) 322 (71.4) 436 (96.7) Fatigue 47 (10.4) 78 (17.3) 125 (27.7) Nausea 41 (9.1) 68 (15.1) 109 (24.2) Decreased ap
Slide 43: Tislelizumab Chemotherapy Combination Data in Lung Cancers
Responses Non - Sq Tislelizumab + pemetrexed + platinum (n=16 Sq Tislelizumab + paclitaxel + platinum (n=15) Sq Tislelizumab + gemcitabine + platinum (n=6) SCLC Tislelizumab + etoposide + platinum (n=17) Total (N=54) BOR, n (%) CR 0 0 0 0 0 PR 5 (31.3) 12 (80.0) 4 (66.7) 8 (47.1) 29 (53.7) UPR 4 (25
Slide 44: Tislelizumab Broad Late-stage Development Program
Phase 3 (n=800) in 2L NSCLC tislelizumab vs. docetaxel Primary endpoint: OS Initiated in Nov. 2017 Pivotal phase 2 (n=70) in R/R cHL tislelizumab monotherapy Primary endpoint: ORR Initiated in Apr. 2017, enrollment completed in 4Q:17, NDA accepted in Aug 2018 Pivotal phase 2 (n=110) in 2L UC tisleli
Slide 45: Pamiparib overview
45 OVERVIEW ▪ Highly selective PARP1 and PARP2 inhibitor with potential brain penetration and strong PARP trapping activity in preclinical studies CLINICAL DATA ▪ Ph1/2 data demonstrated pamiparib was generally well - tolerated with promising anti - tumor activity in ovarian cancer – Low incidence o
Slide 46: Pamiparib Clinical Program
p amiparib + RT/TMZ (PARP + RT/Chemo) Worldwide Worldwide PROGRAM (TARGET) COMMERCIAL RIGHTS 1 DOSE EXPANSION PIVOTAL PH1b PH2* PH2** PH3 DOSE ESC. PH1a pamiparib 1 (BGB - 290, PARP) p amiparib + TMZ (PARP + Chemo) Worldwide Solid tumors Glioblastoma ▪ Two ongoing global Ph1b/2 trials with chemother
Slide 47: Best Change from Baseline in Target Lesions in Ovarian Cancer
(120) (100) (80) (60) (40) (20) 0 20 40 60 80 100 10 mg 80 mg 5 mg 10 mg 60 mg-P2 60 mg-P1 10 mg 60 mg-P2 60 mg-P1 60 mg-P2 60 mg-P2 120 mg 60 mg-P2 80 mg 60 mg-P2 60 mg-P2 60 mg-P2 60 mg-P2 60 mg-P1 60 mg-P2 20 mg 80 mg 60 mg-P2 80 mg 60 mg-P2 60 mg-P2 80 mg 5 mg 60 mg-P2 40 mg 60 mg-P2 2.5 mg 20 m
Slide 48: Pamiparib plus tislelizumab combination data
A. Change in Tumor Volume by Baseline Tumor Type :1 bile duct, 1 peripheral nerve sheath tumor Best Overall Responses Included 1 CR, 3 Confirmed PRs and 7 Unconfirmed PRs ▪ Ovarian or fallopian tube cancer patients (n=29) had best responses of CR (1), PR (2 confirmed, 5 unconfirmed), and SD (7). B r
Slide 49: Thank You
49 Thank You
Slide 50: Supporting Information
50 Supporting Information
Slide 51: BTK Occupancy Is Not Sustained With Ibrutinib
BTK Occupancy Is Not Sustained With Ibrutinib 51 100 9 9 37 68 0 20 40 60 80 100 120 Vehicle 4 hrs 8 hrs 12 hrs 24 hrs Unoccupied BTK (%) 100 0 1 19 27 0 50 100 150 Vehicle 4 hrs 8 hrs 12 hrs 24 hrs Unoccupied BTK (%) 100 0 1 16 62 Vehicle 4 hrs 8 hrs 12 hrs 24 hrs 100 2 9 24 66 Vehicle 4 hrs 8 hrs
Slide 52: Zanubrutinib Achieves Complete and Sustained BTK Occupancy
52 *Data from 20 patients Note: PBMC = Peripheral Blood Mononuclear Cell; Source: Tam et al. ASH 2016 (abstracts 642 and 1216) Zanubrutinib Achieves Complete and Sustained BTK Occupancy in Blood and Lymph Nodes PBMC* Lymph Node ▪ Complete BTK inhibition in PBMCs at the starting dose (40 mg) ▪ Paired
Slide 53: Forecasted Market Size of China PD-1 & PD-L1 Inhibitors
Forecasted Market Size of China PD - 1 & PD - L1 Inhibitors, 2018E - 2030E (Billion USD) BTK • Previous M&A transactions placed high value on the first two BTK inhibitors: • Pharmacyclics , which had half of the economics to ibrutinib, was acquired by AbbVie for $21 billion; and • Acerta , which had