35 slides from Beone Medicines Ltd. Class A's corporate update, Jan 16, 2018
Slide 1: 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 regardin
Slide 2: BeiGene Company Overview
BeiGene Company Overview Founded in 2010 in Beijing as an R&D organization focused on developing best-in-class oncology therapeutics Three proprietary programs: zanubrutinib (BTK inhibitor), tislelizumab (PD-1 antibody) and pamiparib (PARP inhibitor) have initially come from these efforts In the pas
Slide 3: Broad Capabilities in China and Globally
Over 40 clinical trials ongoing or planned for initiation with over 2,000 patients dosed (including 650+ in China) Global clinical team (300+): US (150+), China (140+), AU (10+) Strong relationships with leading KOLs in China and globally Single clinical trials designed for both global and China reg
Slide 4: Experienced Leadership Team
5 Experienced Leadership Team John V. Oyler Founder, CEO, and Chairman Howard Liang, Ph.D. CFO and Chief Strategy Officer Ji Li, Ph.D. EVP, Global Head of Business Development Eric Hedrick, M.D. Chief Advisor Amy Peterson, M.D. Chief Medical Officer, Immuno-oncology Jane Huang, M.D. Chief Medical Of
Slide 5: CFDA Reforms Expected to Make China Integral to Global Oncology Development
CFDA Reforms Expected to Make China Integral to Global Oncology Development and Commercialization Source: CFDA; press research 6 CFDA reforms expand China’s role in global development Reforms expand clinical patient access by removing delays CFDA joined ICH in June 2017 and set international quality
Slide 6: China Commercial Opportunity Expected to Expand Significantly
China Commercial Opportunity Expected to Expand Significantly * Monthly cost is based on NRDL price, PAP not included in calculation as only limited PAP were continued after NRDL inclusion; exchange rate: 1 RMB to 0.15062 dollars. Source: NDRL update, McKinsey Research (September 2017, October 2015)
Slide 7: Near-Term Opportunities Through Collaborations: Celgene
Near-Term Opportunities Through Collaborations Celgene Broad development strategy leverages BeiGene’s China capabilities, while addressing the market opportunity for PD-1, both in China and globally Nine pivotal, global clinical trials planned to run in conjunction with Celgene Focus on four highest
Slide 8: Overview of Zanubrutinib (BGB-3111)
Overview of Zanubrutinib (BGB-3111) Potentially Best-in-Class BTK Inhibitor 9 Overview Development Plan Clinical Data Key Expected Catalysts in 2018 Potential pharmacologic advantages of zanubrutinib could allow for complete, sustained, and selective BTK inhibition in all tissue compartments Develop
Slide 9: Zanubrutinib Clinical Program
Program (Target) Commercial Rights Preclinical Dose Escalation Dose Expansion* Pivotal** Phase 1a Phase 1b Phase 2 Phase 2 Phase 3 Zanubrutinib (BGB-3111) (BTK) Worldwide Zanubrutinib + Gazyva® (BTK + CD20) Worldwide Relapsed / Refractory (R/R) CLL *Some indications will not require a non-pivotal Ph
Slide 10: Zanubrutinib Pharmacokinetics Profile
Adapted from Advani et al., JCO, 2013 Zanubrutinib Pharmacokinetics Profile Cmax and AUC of zanubrutinib at 80mg QD appear to be similar to those of ibrutinib at 560mg Free drug exposure of zanubrutinib at 40mg QD appears to be comparable to that of ibrutinib at 560mg Distinct profile compared to ac
Slide 11: BTK Occupancy Is Not Sustained With Ibrutinib
BTK Occupancy Is Not Sustained With Ibrutinib Potentially better bioavailability and higher exposure of zanubrutinib may allow deeper target suppression in disease-relevant tissues *Animal studies Note: PBMC = Peripheral Blood Mononuclear Cell; Source: BeiGene data and Byrd et al, NEJM, 2013 Ibrutin
Slide 12: Zanubrutinib Complete and Sustained BTK Occupancy
Zanubrutinib Complete and Sustained BTK Occupancy to Date in Blood and Lymph Nodes 13 PBMC* Lymph Node Complete BTK inhibition in PBMCs at the starting dose (40mg) Paired lymph node biopsies were collected during screening or pre-dose on day 3 Median trough occupancy: 100% (160mg BID) vs 94% (320mg
Slide 13: Zanubrutinib Responses in WM
Zanubrutinib Responses in WM Favorable Response to Date in Depth and Durability 14 Source: Trotman et al. 14-ICML (abstract 059) Probability of Progression-free Survival (%) No. of Subjects at Risk Month 42 42 39 31 24 20 18 13 9 4 4 Zanubrutinib PFS in WM 100 90 80 70 60 50 40 30 20 10 0 0 3 6 9 12
Slide 14: Ibrutinib Responses in WM
Ibrutinib Responses in WM 15 Source: Treon et al., NEJM, 2015 Ibrutinib WM n 63 Median time-on-treatment 19.1 months Best Response CR VGPR PR MR SD/PD 0 10 (16%) 36 (57%) 11 (17%) 6 (10%) IgM reduction (median, %) 35.2 g/L to 8.8 g/L (75%) Hemoglobin change (median) 105 g/L to 138 g/L Probability of
Slide 15: Zanubrutinib Responses in CLL
Zanubrutinib Responses in CLL Highly Active With Encouraging Response Durability 16 Source: Seymour et al. 14-ICML 2017 (abstract 237) poster 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%)
Slide 16: Ibrutinib Responses in CLL
Ibrutinib Responses in CLL 17 Source: For TN, Burger, et al New Engl J Med 2015. For R/R, Byrd, et al New Engl J Med 2013 Ibrutinib Responses in R/R CLL Ibrutinib TN TN CLL 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 Ibrutinib R/R CLL n 85 Med
Slide 17: Ibrutinib Discontinuation for Toxicity or Progression in CLL
Ibrutinib Discontinuation for Toxicity or Progression in CLL 18 Treatment-Naïve (n=80) Relapsed/ Refractory (n=536) Median Follow up 14.5 months Total Treatment D/C 19 (24%) 231 (43%) Toxicity/ Tolerability 12 (15%) 117 (22%) CLL Progression 3 (4%) 49 (9%) Transformation (RT or HD) 0 (0%) 10 (2%) De
Slide 18: Zanubrutinib Discontinuation in CLL Is Uncommon
Zanubrutinib Discontinuation for Toxicity or Progression in CLL Is Uncommon 19 Treatment-Naïve (n=18) Relapsed/ Refractory (n=51) Median Follow up 10.3 months Total Treatment D/C 0 (0%) 2 (4%) Toxicity/ Tolerability 0 (0%) 1 (2%) CLL Progression 0 (0%) 0 (0%) Transformation (RT or HD) 0 (0%) 1 (2%)
Slide 19: Zanubrutinib Tolerability to Date
Zanubrutinib Tolerability in Over 600 Patients to Date AE of Interest (All Causes) Zanubrutinib (Including Patients Enrolled in Combo Studies) Patient Number N = 641 Mean Exposure Time 7.7 mo Atrial Fibrillation 1.7% Serious Hemorrhage 1.9% AE of Interest (All Causes) Zanubrutinib (Single Agent Only
Slide 20: Zanubrutinib Plus Obinutuzumab Combination in Follicular Lymphoma
Zanubrutinib Plus Obinutuzumab Combination in Follicular Lymphoma 21 Overall response rate and complete responses to date compare favorably to those achieved with respective single-agents and recently approved therapies FL^ Zanubrutinib + Obinutuzumab1 Zanubrutinib2 Ibrutinib3 Obinutuzumab4 Idelalis
Slide 21: Zanubrutinib Responses Across Multiple B-Cell Malignancies
22 Zanubrutinib Responses Across Multiple B-Cell Malignancies Zanubrutinib TN CLL R/R CLL WM MZL MCL FL DLBCL Source 14-ICML 14-ICML 14-ICML ASH17 ASH17 ASH17 ASH17 n 16 50 42 9 32 17 26 Follow-up (med) 7.6 mo 14.0 mo 12.3 mo 7.0 mo 9.5 mo 7.8 mo 4.2 mo Prior Lines (med) 0 2 (1-7) 1 (1-8) 2 (1-8) 2
Slide 22: Broad Clinical Development Plan for Zanubrutinib
Broad Clinical Development Plan for Zanubrutinib First NDA Filing in China Expected in 2018 Global Monotherapy China Global Combination CLL, WM, MCL, DLBCL, FL, MZL, HCL, RT B-cell Malignancies Phase 1b zanubrutinib + G*** CLL, FL, DLBCL, NHL Phase 1b zanubrutinib+tislelizumab FL, DLBCL, primary CNS
Slide 23: Tislelizumab (BGB-A317) Development Program
Tislelizumab (BGB-A317) Broad Global and China-Focused Development Program 24 Overview Development Plan Clinical Data Expected 2018 Catalysts Tislelizumab is a PD-1 checkpoint inhibitor currently under development in a wide range of solid tumor indications Potential differentiation from approved PD-
Slide 24: Tislelizumab Clinical Program
Program (Target) Commercial Rights Preclinical Dose Escalation Dose Expansion* Pivotal** Phase 1a Phase 1b Phase 2 Phase 2 Phase 3 Tislelizumab (BGB-A317) (PD-1) Worldwide (Heme Malignancies); Asia ex-Japan (Solid Tumors)1 Tislelizumab + Pamiparib (PD-1 + PARP) Worldwide Tislelizumab + Zanubrutinib
Slide 25: Anti-PD-1 Antibody Therapies Represent a Large Market Opportunity
Anti-PD-1 Antibody Therapies Represent a Large Market Opportunity, Particularly in China Source: LEK Analysis, Data from World Health Organization (2012); Chen et al., CA Cancer J Clin, 2016; SEER.cancer.gov ¹ China data is from 2015, U.S. data is from 2017, EU5 data is from 2012, Japan data is from
Slide 26: Tislelizumab Phase 1 Data Demonstrated Clinical Activity
27 Tislelizumab Phase 1 Data Demonstrated Proof of Principle and Clinical Activity Note: 93 pts included in the chart, the remaining 6 pts were not evaluable for target lesion response based on imaging assessment at the cutoff time Source: 1 Phase 1 data as of September 30, 2016, presented at the So
Slide 27: Tislelizumab Data by Tumor Type
28 Tumor Type Gastric Cancer Esophageal Cancer Head & Neck SCC Ovarian Cancer Hepatocellular Carcinoma Median Treatment Duration 45 days (4-457) 50 days (1-246) 104 days (30-339) 71 days (29-540) 64 days (1-471) Evaluable Patients N=34 N=31 N=17 N=50 N=27 PR Confirmed Unconfirmed 4 -- 2 3 3 -- 2 --
Slide 28: Tislelizumab Global Clinical Trial Plan With Celgene
Tislelizumab – Broad, Global Clinical Trial Plan in Collaboration With Celgene for Multiple Solid Tumors 29 NSCLC Esophageal Gastric 1L Setting / Early Stage Disease Celgene-led trials (planned) BeiGene-led trials (planned) Ongoing trials 2L/3L Setting HCC Stage III CRT combination options 2L tislel
Slide 29: Pamiparib (BGB-290) Selective Inhibitor of PARP1 and PARP2
Pamiparib (BGB-290) Selective Inhibitor of PARP1 and PARP2 30 Overview Development Plan Clinical Data Expected 2018 Catalysts Highly selective PARP1 and PARP2 inhibitor with significant brain penetration and strong PARP trapping activity in preclinical studies Two ongoing global Phase 1b/2 trials wi
Slide 30: Pamiparib Monotherapy Phase 1/2 Data
31 Pamiparib Monotherapy Phase 1/2 Data Promising Activity and Generally Well-Tolerated to Date Source: Phase 1/2 data as of June 1, 2017, presented at the ESMO 2017 meeting (Lickliter et al) Best Change from Baseline in Target Lesions in Epithelial Ovarian Cancer and Other Associated Tumors Summary
Slide 31: Tislelizumab/Pamiparib Combination Escalation Data
A. Change in Tumor Volume by Baseline Tumor Type Tislelizumab/Pamiparib Combination Escalation Data Generally Well-Tolerated With Preliminary Anti-Tumor Activity in Multiple Tumor Types :1 bile duct, 1 peripheral nerve sheath tumor Best overall responses included 1 CR, 3 confirmed PRs and 7 unconfir
Slide 32: Expected Timing of Near-Term Events
33 Event Expected Timing Zanubrutinib (BTK Inhibitor) Present updated Phase I monotherapy or combination data at a medical conference Present China pivotal trial data Initiate head-to-head Phase 3 trial versus ibrutinib in R/R CLL NDA submission in China Completion of global WM registrational trial
Slide 33: Pipeline Programs and Commercial Rights
Program (Target) Commercial Rights Current Phase Lead Indications Phase 1 Phase 2* Pivotal Phase 2** Phase 3 Zanubrutinib (BGB-3111, BTK) Worldwide WM, 1L CLL R/R MCL, R/R CLL, WM Zanubrutinib + Gazyva® (BTK + CD20) Worldwide R/R FL Tislelizumab (BGB-A317, PD-1) Worldwide for hem malignancy, Asia ex
Slide 34: Conclusion – BeiGene Company Highlights
Conclusion – BeiGene Company Highlights 850+ person, global biotech company rooted in China with research, development, manufacturing, and commercial capabilities Ability to leverage regulatory changes in China as the country becomes an integral component of novel drug development and the oncology d
Slide 35: Conclusion — BeiGene Company Highlights
Conclusion — BeiGene Company Highlights ™ 850+ person, global biotech company rooted in China with research, development, manufacturing, and commercial capabilities ® Ability to leverage regulatory changes in China as the country becomes an integral component of novel drug development and the oncolo