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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
_____________________
Form 8-K
_________________________
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event Reported): August 25, 2021

BEIGENE, LTD.
(Exact Name of Registrant as Specified in Charter)
Cayman Islands
001-37686
98-1209416
(State or Other Jurisdiction of Incorporation)
(Commission File Number)
(I.R.S. Employer Identification Number)
c/o Mourant Governance Services (Cayman) Limited
94 Solaris Avenue, Camana Bay
Grand Cayman KY1-1108
Cayman Islands
(Address of Principal Executive Offices) (Zip Code)
+1 (345) 949-4123
(Registrant's telephone number, including area code)
Not Applicable
(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
American Depositary Shares, each representing 13 Ordinary Shares, par value $0.0001 per share BGNE The NASDAQ Global Select Market
Ordinary Shares, par value $0.0001 per share* 06160 The Stock Exchange of Hong Kong Limited
*Included in connection with the registration of the American Depositary Shares with the Securities and Exchange Commission. The ordinary shares are not registered or listed for trading in the United States but are listed for trading on The Stock Exchange of Hong Kong Limited.
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2). Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o





Item 8.01. Other Events.

BeiGene, Ltd. (the “Company”) hosted an investor conference call and webcast to discuss the Company’s early development pipeline and research on August 25, 2021. A copy of the Company’s presentation used during the conference call and webcast is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

Exhibit No. Description
99.1
Company Presentation dated August 25, 2021
104 The cover page from this Current Report on Form 8-K, formatted in Inline XBRL




Exhibit Index
 
Exhibit No. Description
99.1
104 The cover page from this Current Report on Form 8-K, formatted in Inline XBRL
 



SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
  BEIGENE, LTD.
     
     
Date: August 26, 2021 By:  /s/ Scott A. Samuels        
  Name: Scott A. Samuels
  Title: Senior Vice President, General Counsel


1 August 25, 2021 R & D U P DAT E Exhibit 99.1


 
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 statements regarding BeiGene’s research, discovery, and pre-clinical and early-stage clinical programs and plans; recent clinical data for BeiGene’s product candidates and approvals of its medicines; the conduct of late-stage clinical trials and expected data readouts; additional planned commercial product launches; and the advancement of and anticipated clinical development, regulatory milestones and commercialization of BeiGene’s medicines and drug candidates. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and medicines; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates and achieve and maintain profitability; the impact of the COVID-19 pandemic on BeiGene’s clinical development, commercial, regulatory and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent periodic report filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the SEC. All information in this presentation is as of the date of this presentation, and BeiGene undertakes no duty to update such information unless required by law. Some of the clinical data in this presentation relating to BeiGene’s investigational drug candidates is from pre-clinical studies or early phase, single-arm clinical trials. When such data or data from later stage trials are presented in relation to other investigational or marketed drug products, the presentation and discussion are not based on head-to-head trials between BeiGene’s investigational drug candidates and other products unless specified in the trial protocol. BeiGene is still conducting pre-clinical studies and clinical trials and, as additional patients are enrolled and evaluated, data on BeiGene’s investigational drug candidates may change. This presentation and the accompanying oral presentation contain data and information obtained from third-party studies and internal company analysis of such data and information. BeiGene has not independently verified the data and information obtained from these sources. Forward-looking information obtained from these sources is subject to the same qualifications noted above.


 
3 TODAY’S AGENDA Welcome and Introduction: Creating an Ecosystem of Innovation John V. Oyler Our Scientific Ecosystem of Excellence Xiaodong Wang R&D Capability and Portfolio Overview Lai Wang, Ph.D. Hematology Oncology Clinical Program Update William Novotny, M.D. Solid Tumor Clinical Program Update Yong (Ben) Ben, M.D. New Modalities and Future Pipeline Lai Wang, Ph.D. The Road Ahead John V. Oyler Questions and Answers


 
4 CREATING AN ECOSYSTEM OF INNOVATION John V. Oyler Co-Founder, Chairman and CEO


 
5 Help transform the biotechnology industry, creating impactful medicines that will be affordable and accessible to far more cancer patients around the world through science and business innovation OUR MISSION: PATIENTS FIRST THROUGH SCIENCE AND AFFORDABILITY


 
6 WE SAW THE ONCE-IN-A-LIFETIME OPPORTUNITY TO ACCELERATE GLOBAL DEVELOPMENT 10+ YEARS AGO… Internal, global, and modernized efficiency of clinical science to create time and cost advantages and broaden patient access


 
7 BUILDING A GLOBAL ECOSYSTEM OF COST AND SPEED COMPETITIVE ADVANTAGES Innovation with speed and lower cost to better serve patients around the world FULLY INTEGRATED END-TO-END ~7,000 COLLEAGUES - 5 CONTINENTS - 17 GEOGRAPHIES • One of world’s largest oncology teams (650+) with 50+ preclinical programs • Passionate, entrepreneurial science-based culture • Internal team (not CROs) • 1,700+ internal clinical development colleagues, predominately CRO-free • More inclusive development (e.g., Australia, China, Poland) enabling ~ 1/3 cost & time savings • ~50 assets in clinical & commercialization stage • 2,900+ in China, competitively positioned, science-based leadership • 150+ competitive footprint in U.S. • Expanding presence in multiple countries/regions, including underserved areas • In-house capabilities bring cost, agility, and flexibility to internal and external programs • Built to state-of-the-art standards & technologies (e.g., 1st paperless facility in China) • Building toward 200,000 L of biologics capacity in Guangzhou


 
8 Xiaodong Wang, Ph.D. Co-Founder & Chairman of Scientific Advisory Board OUR SCIENTIFIC ECOSYSTEM OF EXCELLENCE


 
9 RESPONDING TO GREATEST PATIENT NEED Estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths in 2020 worldwide Our broad pipeline covers 80% of the world’s cancers by incidence Head and Neck GBM NSCLC SCLC ESCC GC Bladder Prostate Sarcoma Melanoma BC CRC Ovarian Cervical HCC BTC HL NHL Leukemia Source: ASC Journals


 
10 TO REACH BILLIONS OF PATIENTS WORLDWIDE


 
11 Lai Wang, Ph.D. Global Head of R&D R&D CAPABILITY AND PORTFOLIO OVERVIEW


 
12 R&D HIGHLIGHTS R&D Engine Built at Scale to Fuel Innovation with Efficiency and Quality ‣ Highly productive preclinical research team with proven track record experienced major expansion recently ‣ Clinical development is largely CRO-free, with unique global operating model Robust Innovative Pipeline Focusing on Internal Combinations ‣ Close to 100 programs, including 50+ at preclinical stage, 30+ at clinical stage and 10+ at commercial stage ‣ Strong heme and solid tumor franchise anchored on BTK and PD-1 programs


 
13 SCIENCE-DRIVEN PRECLINICAL CAPABILITIES EXPERIENCED MAJOR EXPANSION RECENTLY Evolution Through Two Stages Stage 1: Establishing Core Capabilities andTalent for Early Success (2011-2018) ‣ 150-200 scientists ‣ Proven track-record with 3 internally discovered, commercially available medicines ‣ Small scale, only 1-2 clinical candidates a year Stage 2: Expanding New Capabilities and Talent for Future Success (2019 – Present) ‣ 650+ scientists now growing to 800 by end of 2021 ‣ Investing in new platforms and capabilities and driving efficiencies through portfolio management ‣ 50+ preclinical programs, ~50% with first-in-class potential ‣ A burst of new clinical molecules expected in the next few years New Platforms/Capabilities HTS Screen Virtual Screen CDAC ADC Single B Cell Single Domain Ab Common Light Chain Bioinformatics Functional Genomics Pre- formulation Process Research Biologics Early CMC CDAC, Chimeric Degradation Activating Compound; ADC, Antibody Drug Conjugate.


 
14 AN INTERNAL CLINICAL DEVELOPMENT TEAM EQUIPPED TO RUN GLOBAL DEVELOPMENT AT SCALE ‣ Through the extensive internalization effort in the last few years, we are now largely CRO- free, allowing better control over quality, speed, cost and site / PI engagement ‣ Currently 1,700+ global clinical development colleagues, close to 700 outside of China, growing to 2,000+ by end of 2021 ‣ Internal training academy allows for continuous growth of the team and promotes quality and efficiency ‣ 95+ clinical trials initiated since 2013 in 40+ geographies ‣ 13,000+ patients and healthy volunteers enrolled, close to half outside of China 42 Americas trials EMEA 28 trials Greater China 59 trials APAC ex-China 52 trials Strong Internal Global Development Capabilities BeiGene’s Global Clinical Trial Footprint


 
15 UNIQUE OPERATING MODEL TO DRIVE SPEED & COST ADVANTAGE Source: Grants Manager median benchmark data for those countries in which BeiGene has enrolled at least one patient. Each region/country is weighted for the number patients enrolled to date. 31% 33% 41% 60% 91% 100% 0 10000 20000 30000 40000 50000 60000 70000 80000 90000 Eastern Europe China ANZ/ SK Western Europe Japan United States Investigator Fee Per Patient 0.33 0.35 0.49 0.53 0.55 0.69 0.91 Clinical Trial Enrollment Rate (Pts/Site/Month) Benchmark (NSCLC 1L) BeiGene 1L NSCLC studies China ANZ/SK United States Western Europe Eastern Europe Japan BeiGene’s China-only 1L NSCLC Phase 3 Studies Source: Internal data on file; Benchmark from Citeline, filtered for NSCLC 1L studies. Includes data only from the same countries that BeiGene has run clinical studies. Data exported on 9 Aug 2021 ANZ/ SK, Australia and New Zealand/ Slovakia Americas APAC ex-China EU 53% 21% 17% 9% BeiGene Trial Subjects Source: Internal tracking. Inclusive of all subjects ever enrolled in BeiGene studies as of 30 June 2021 China Speed Cost efficiency Global vision High quality China-inclusive, fully integrated, global development capabilities


 
16 BRAF BTK (approved) PARP (approved) PD-1 (approved) 1st Wave (2013-2015) PD-L1 TIM-3 TIGIT BCL-2 OX40 PI3Kδ RAF Dimer 2nd Wave (2016-2020) New Waves (2021 and beyond) TRANSLATING SCIENCE INTO BETTER AND NOVEL MEDICINES Proven track record: our first decade SM, Small Molecule; mAb, Monoclonal Antibody; ADC, Antibody Drug Conjugate; TAA, Tumor Associated Antigen; CDAC, Chimeric Degradation Activating Compound; BsAb, Bispecific Antibody; TsAb, Trispecific Antibody; CAR-NK, Chimeric Antigen Receptor-Natural Killer Cell HPK-1 Pro-Cytokine BsAb/TsAb • 10+ new programs Commercial Clinical Preclinical SM and mAb • 20+ new programs CDAC • BTK, total 7+ programs ADC • 10+ TAAs Cell therapy • CAR-NK and more mRNA therapy


 
17 ENHANCING INNOVATION AND ACCESS THROUGH COLLABORATION We follow the science virtually anywhere that leads to innovation – independently and via collaboration Extend our existing franchise in large indications tisle combinations: +sitra; +zanidatamab; +Leap asset NOVEL COMBINATIONS ADC mRNA NEXT-GEN TECHNOLOGIES “Partnering with BeiGene was a key component of our development and commercialization strategy for ZW25 and ZW49. This collaboration allows Zymeworks to leverage BeiGene’s resources and expertise to accelerate the development of our most advance product candidates and broaden our reach globally including in a key region of the world.” ALI TEHRANI President and CEO of Zymeworks “BeiGene is evaluating sitravatinib in patients with a variety of tumor types with the goal of accelerating development of treatment options for more patients. Our collaboration with BeiGene has supported the expansion of our world-wide development capabilities by leveraging their clinical expertise in China.” CHARLES M. BAUM, M.D., Ph.D. President and CEO of Mirati Therapeutics ADC, Antibody Drug Conjugate; CAR-NK, Chimeric Antigen Receptor-Natural Killer Cell CAR-NK Bispecifics


 
18 DEEP CLINICAL AND COMMERCIAL PIPELINE *Selected assets and indications are presented. **Some indications will not require a non-pivotal Ph2 clinical trial prior to beginning pivotal Ph2 or Ph3 clinical trials. ***Confirmatory clinical trials post approval are required for accelerated or conditional approvals. ^ BiTE, ^^ HLE BiTE, † Novartis owns commercial rights in United States, Canada, Mexico, the European Union, United Kingdom, Norway, Switzerland, Iceland, Liechtenstein, Russia, and Japan. †† ABX is suspended in China. ††† Mirati is also conducting its own clinical studies with sitravatinib, including the Phase 3 SAPPHIRE trial in non-Sq NSCLC. †††† ZW25, AML: acute myeloid leukemia, HLE BiTE: Half-life extended Bi-specific T-cell engagers, BC: breast cancer, GC/GEJ: gastric cancer/gastroesophageal junction, HCC: hepatocellular carcinoma, IND: Investigational New Drug, MEL: melanoma, MM: multiple myeloma, NHL: non- Hodgkin’s lymphoma, N/SCLC: non-/small cell lung cancer, OC: ovarian cancer, RCC: renal cell carcinoma, SM: small molecule; 1. By MapKure, a JV with SpringWorks. COMPOUND DOSE ESC. DOSE EXPANSION PIVOTAL FILED / MARKETED COMMERCIAL RIGHTS PARTNER PH1a PH1b PH2* PH2** PH3 Zanubrutinib (BTK) MCL, WM, CLL/SLL, MZL, FL (Phase 2), Lupus (Phase 2), DLBCL (Phase 1) Global Tislelizumab (PD-1) MSI-H or dMMR solid tumors, ESCC, HCC, NSCLC, cHL, UC, NK/T-cell lymphoma (Phase 2), solid tumors, B-cell malignancies (combo; Phase 1) Global ex-NVS territory† Novartis Pamiparib (PARP) gBRCA+ OC, PSOC (Phase 3), HER2- BRCA+ BC (Phase 2), Glioblastoma (Phase 2), Solid tumors (Phase 1) Global BGB-A1217 (TIGIT) NSCLC, Cervical Cancer (Phase 2), ESCC (Phase 2), Solid tumors (Phase 1) Global BGB-A445 (OX40) Solid tumors Global BGB-A425 (TIM-3) Solid tumors Global BGB-A333 (PD-L1) Solid tumors Global BGB-11417 (BCL-2) B-cell malignancies Global BGB-15025 (HPKI) Advanced solid tumors Global BGB-10188 (PI3Kδ) B-cell malignancies, Solid tumors Global Lifirafenib (RAF dimer) B-RAF/K-RAS/N-RAS mut. Solid tumors Global REVLIMID MM China Bristol Myers Squibb ABRAXANE†† BC, NSCLC, Pancreas adenocarcinoma VIDAZA Myelodysplastic Syndromes SYLVANT Multicentric Castleman's disease China EUSA Pharma QARZIBA Neuroblastoma BAT1706 Metastatic colorectal cancer China BIO-THERA Sitravatinib††† (multi-kinase inhibitor) NSCLC, RCC, OC, MEL, HCC, GC/GEJC Asia ex-Japan, AU, NZ Mirati Therapeutics Zanidatamab†††† (HER2, bispecific antibody) BC, GEA, Biliary track (Phase 3) Asia ex-Japan, AU, NZ Zymeworks ZW49 (HER2, bispecific ADC) HER2+ cancers Asia ex-Japan, AU, NZ Zymeworks BGB-3245 (B-RAF) Solid tumors Asia ex-Japan SpringWorks1 SEA-CD70 (CD70) MDS, AML Asia ex-Japan, AU, NZ Seattle Genetics DKN-01 (DKK1) GC/GEJC Asia ex-Japan, AU, NZ Leap Therapeutics ABI-H0731 (HBV core inhibitor) Chronic Hepatitis B Virus China Assembly BioABI-H2158 (HBV core inhibitor) Chronic Hepatitis B Virus ABI-H3733 (HBV core inhibitor) Chronic Hepatitis B Virus COMPOUND DOSE ESC. DOSE EXPANSION PIVOTAL FILED / MARKETED COMMERCIAL RIGHTS PARTNER PH1a PH1b PH2* PH2** PH3 BLINCYTO® ALL China Amgen KYPROLIS® MM XGEVA® MM, Solid tumors LUMAKRAS (KRAS G12C) Solid tumors, NSCLC, CRC Pavurutamab^^ (BCMA x CD3) MM AMG 176 (MCL-1) Myeloid malignancies AMG 330^ (CD33 x CD3) Myeloid malignancies AMG 673^^ (CD33 x CD3) AML AMG 427^^ (FLT3 x CD3) AML Tarlatamab^^ (DLL3 x CD3) SCLC, Neuroendocrine Prostate Cancer Acapatamab^^ (PSMA x CD3) Prostate Cancer, NSCLC AMG 509 (STEAP1 XmAb ® antibody) mCRPC AMG 506 (FAP x 4-1BB, DARPin ® ) Solid tumors AMG 256 (PD1 x IL12 mutein) Solid tumors AMG 650 (KIF18A) Solid tumors AMG 910^^ (CLDN18.2 x CD3) GC/GEJC AMG 199^^ (MUC17 x CD3) GC/GEJC AMG 994 Solid tumors AMG 397 (MCL-1) Myeloid malignancies


 
19 William Novotny, M.D. Head of Clinical Development, Hematology HEMATOLOGY ONCOLOGY CLINICAL PROGRAM UPDATE


 
20 Lymphoma/CLL Zanubrutinib (BTK) Tislelizumab (PD-1) Ociperlimab (TIGIT) BGB-11417 (BCL-2) BGB-10188 (PI3Kδ) REVLIMID SYLVANT (IL-6) AML/MDS/ALL BGB-11417 (BCL-2) BGB-A425 (TIM-3) VIDAZA BLINCYTO(R) (CD19 x CD3) AMG 330/673 (CD33 x CD3) AMG 427 (FLT3 x CD3) AMG 176/397 (MCL-1) SEA-CD70 (CD70) BGB-11417 (BCL-2) REVLIMID XGEVA(R) (RANKL) KYPROLIS(R) AMG 701 (BCMA x CD3) AMG 176/397 (MCL-1) Myeloma Global Rights Regional Rights SUMMARY OF HEMATOLOGY CLINICAL AND COMMERCIAL PORTFOLIO Tislelizumab


 
21 BEST-IN-CLASS BTK INHIBITOR Designed to Overcome Shortcomings of Other BTK Inhibitors Superiority Over Ibrutinib in Clinic Broad Indications Approved/In Development ‣ Reduced off-target toxicity ‣ Achieved sustained target inhibition in disease originating tissues ‣ Better efficacy ‣ Better safety ‣ More convenient ‣ CLL ‣ MCL ‣ WM ‣ MZL ‣ FL


 
22 BETTER KINASE SELECTIVITY THAN IBRUTINIB, ACALABRUTINIB AND ITS METABOLITE M27 Zanubrutinib Ibrutinib Acalabrutinib M27 – Acala’s Metabolite ‣ Kinome analysis (370 kinases panel) at concentrations of 100 times of each molecule’s IC50 for BTK (not at 1 µM which is not adjusted for BTK potency); acalabrutinib and its metabolite M27 are much weaker BTK inhibitors ‣ Zanubrutinib demonstrated better kinase selectivity (7 off-target kinases with >50% inhibition) compared to ibrutinib (17), acalabrutinib (15), and M27 (23) at 100X IC50 BTK IC50 was generated by RBC (Reaction Biology Corp.)


 
23 FAVORABLE PHARMACOKINETIC PROFILE COMPARED TO ACALABRUTINIB AND IBRUTINIB FREE DRUG CONCENTRATION TIME PROFILES RELATIVE TO IC50 Zanubrutinib Ibrutinib 560 mg QD Acalabrutinib 100 mg BID Note: These data are from separate analyses. Limitations of cross-trial comparisons apply. Source: 1. Kaptein, et al. Blood. 2018;132:1871. 2. Ou, et al. Leuk Lymphoma. In press. 3. Marostica, et al. Cancer Chemother Pharmacol. 2015;75:111-121.0 QD, Once a Day; BID, Twice a Day


 
24 BROAD CLINICAL DEVELOPMENT PROGRAMS ACROSS MULTIPLE HEMATOLOGIC MALIGNANCIES AND BEYOND ONCOLOGY CLL/SLL WM MCL MZL DLBCL FL Mixed heme malignancies Non- oncology Company Sponsored > 1,100 > 300 >175 >100 >125 >250 Investigator P2 P2P3 P3 P2P2P3 P3 P2 P1P2 P2 P1P2 P1 P1 P2 P1P2 P2 P2 P2 P2 P2 P2 P2 P2 P2P2 P2 P1 P1 P2 P2 P2 P2 1PHASE 2PHASE 3PHASE Vs. Ibrutinib P3 P2 Zanubrutinib Patients P2 P2P2 Note: Countries with approvals, filings and trials on-going are included.


 
25 ZANUBRUTINIB VS. BENDAMUSTINE + RITUXIMAB: STATISTICALLY SIGNIFICANT IMPROVEMENT IN PFS DEMONSTRATED IN TREATMENT-NAÏVE CLL/SLL PATIENTS Treatment Naïve CLL/SLL without del(17p) (N=479) Zanubrutinib 160mg PO BID until PD (n=241) Bendamustine + Rituximab x 6 (n=238) R (1:1) for CLL/SLL Patients Study Identifier: BGB-3111-304, NCT03336333 Primary Endpoints: PFS by IRC in Cohort 1 Key Secondary Endpoints: Cohort 1 – ORR, OS, DOR, safety Source: BeiGene press release on 2021 June (https://ir.beigene.com/news-details/?id=cbcd1204-96c4-44f3-a956-0a6d55b821b8). PO, Oral; BID, Twice a Day; PD, Disease Progression


 
26 ZANUBRUTINIB VS. IBRUTINIB: SUPERIORITY IN OVERALL RESPONSE RATE BY INVESTIGATOR ASSESSMENT DEMONSTRATED IN RELAPSED OR REFRACTORY CLL/SLL PATIENTS for CLL/SLL Patients The PFS and OS analyses were not pre-specified. More results including safety data were presented at EHA 2021. Hillmen P et al. Abstract LB1900. ORR, Overall Response Rate; CR, Complete Response; PR, Partial Response; PFS, Progression-Free Survival; OS, Overall Survival Study Identifier: BGB-3111-305, NCT03734016 Primary Endpoints: ORR by Investigator Assessment Key Secondary Endpoints: PFS, OS, safety ORR by Investigator Assessment PFS by Investigator Assessment Overall Survival Zanubrutinib (n=207) Ibrutinib (n=208) Primary endpoint: ORR (PR+CR) 78.3% 62.5% P<0.001 CR/CRi 1.9% 1.4% PR 75.8% 61.1% ORR (PR-L+PR+CR) 88.4% 81.3% 12 Months PFS Ibrutinib 84% Zanubrutinib 94.9% P=0.0007 12 Months OS Ibrutinib 92.7% Zanubrutinib 97% P=0.1081


 
27 for CLL/SLL Patients ZANUBRUTINIB LONG-TERM FOLLOW-UP: DEEP AND DURABLE RESPONSES IN PATIENTS WITH RELAPSED OR REFRACTORY CLL/SLL Study Identifier: BGB-3111-AU-003, NCT02343120 Primary Endpoints: safety, RP2D Key Secondary Endpoints: ORR, CR rate, PR rate, PFS, OS, DOR Best Overall Response Source: Internal data on file PR2D, Recommended Phase 2 Dose; DOR, Duration of Response PFS PFS at 24 Months: 90.6% (95% CI: 82.7-95.0) PFS at 36 Months: 82.8% (95% CI: 72.9-89.3) Investigator-Assessed Response N = 103 ORR (PR + CR) 90.3% ORR (PR-L or better) 94.2% Phase 1 B-Cell Malignancies BGB-3111-AU003 Median Follow-up: 39.4 Months (95% CI: 33.9-44.9 )


 
28 Phase 2 Relapsed/Refractory MCL BGB-3111-206 for MCL Patients ZANUBRUTINIB LONG-TERM FOLLOW-UP: DEEP AND DURABLE RESPONSES IN PATIENTS WITH RELAPSED OR REFRACTORY MCL Best Overall Response by IRC More results including safety data were presented at EHA 2021. Song Y, et al. Abstract EP789. Median PFS = 33 month (95% CI: 19.4, NE) Study Identifier: BGB-3111-206, NCT03206970 Primary endpoint: ORR by IRC Secondary endpoints: PFS, DOR, TTR Response by IRC N=86 ORR (CR+PR) 83.7% Best Response CR 77.9% PR 5.8%


 
29 ZANUBRUTINIB VS. IBRUTINIB: DIRECTIONALLY FAVORABLE VGRP+CR RATE AND PFS/OS OBSERVED IN MYD88MUT WALDENSTRÖM MACROGLOBULINEMIA PATIENTS for WM Patients †Adjusted for stratification factors and age group. †† Adjusted for stratification factors and age group. p-value is for descriptive purpose only. More results including safety data were presented at: 1) ASCO 2020. Tam CS et. al. Abstract S225. 2) EHA 2020. Dimopoulos M et al. Abstract EP1180. VGPR, Very Good Partial Response Study Identifier: BGB-3111-302, NCT03053440 Primary Endpoints: CR and VGPR by IRC Key Secondary Endpoints: MRR(CR+VGPR+PR), DOR, PFS, Safety CR+VGPR PFS by IRC OS Ibrutinib 87.2% Event Free Rates at 12 Months Zanubrutinib 89.7% Ibrutinib 93.9% Event Free Rates at 12 Months Zanubrutinib 97.0% IRC Zanubrutinib Ibrutinib 28.4% 19.2% CR+VGPR Rate difference = 10.2† (-1.5, 22.0) p-value = 0.0921 INVESTIGATOR Zanubrutinib Ibrutinib 28.4% 17.2% CR+VGPR Rate difference = 12.1 † † (0.5, 23.7) p-value = 0.0437


 
30 Safety Outcomes 1) EHA 2021. Hillmen P et al. Abstract LB1900. 2) EHA 2020. Dimopoulos M et al. Abstract S225. ZANUBRUTINIB VS. IBRUTINIB: IMPROVED TOLERABILITY OF ZANUBRUTINIB COMPARED TO IBRUTINIB Category, n(%) Zanubrutinib (n=204) Ibrutinib (n=207) Any AE 195 (95.6) 205 (99.0) Grade ≥3 AE 114 (55.9) 106 (51.2) Serious AE 56 (27.5) 67 (32.4) AE leading to death 8 (3.9) 12 (5.8) AE leading to dose reduction 23 (11.3) 25 (12.1) AE leading to dose interruption 81 (39.7) 84 (40.6) AE leading to treatment discontinuation 16 (7.8) 27 (13.0) Category, n(%) Zanubrutinib (n=101) Ibrutinib (n=98) Patients with ≥1 AE 98 (97.0) 97 (99.0) Grade ≥3 AE 59 (58.4) 62 (63.3) Serious AE 40 (39.6) 40 (40.8) AE leading to death 1 (1.0) 4 (4.1) AE leading to dose reduction 14 (13.9) 23 (23.5) AE leading to dose interruption 47 (46.5) 55 (56.1) AE leading to treatment discontinuation 4 (4.0) 9 (9.2)


 
31 Safety Outcomes ZANUBRUTINIB VS. IBRUTINIB: FAVORABLE AFIB/FLUTTER OUTCOMES Atrial Fibrillation/Flutter Atrial Fibrillation/Flutter Hypertension Ibrutinib 10.1% Zanubrutinib 2.5% P value = 0.0014 Ibrutinib 15.3% P value = 0.0008 Zanubrutinib 2.0% P value = 0.0016 Zanubrutinib 10.9% Ibrutinib 17.3% More results including safety data were presented at: 1) EHA 2021. Hillmen P et al. Abstract LB1900. 2) EHA 2020. Dimopoulos M et al. Abstract S225.


 
32 FAVORABLE CLINICAL PHARMACOLOGY PROFILE PROVIDES CLINICAL CONVENIENCE FOR PATIENTS 1. Brukinsa USPI 2019. 2. Ying C Ou et al. Rationale for once-daily or twice-daily dosing of zanubrutinib in patients with mantle cell lymphoma, Leuk Lymphoma. 2021 3. Kun Wang et al. Comprehensive PBPK model to predict drug interaction potential of Zanubrutinib as a victim or perpetrator, CPT Pharmacometrics Syst Pharmacol. 2021 4. Song Mu et al. Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects, Cancer Chemother Pharmacol. 2019 5. Ying C Ou et al. Population Pharmacokinetic Analysis of the BTK Inhibitor Zanubrutinib in Healthy Volunteers and Patients With B-Cell Malignancies, Clin Transl Sci. 2021 6. Ying C Ou et al. Evaluation of drug interaction potential of zanubrutinib with cocktail probes representative of CYP3A4, CYP2C9, CYP2C19, P-gp and BCRP, Br J Clin Pharmacol. 2020 7. Ying C Ou et al. A phase 1, open-label, single-dose study of the pharmacokinetics of zanubrutinib in subjects with varying degrees of hepatic impairment, Leuk Lymphoma. 2020 Flexible dosing regimen Less drug-drug interactions (DDI); ability to be safely and effectively co-administered with a broader variety of concomitant medicines Improved safety for organ -dysfunctional patients (1, 5, 7) ‣ Can be administered as QD or BID (1, 2) ‣ Can be administered with or without food (1) ‣ Can be co-administered with strong or moderate CYP3A inhibitors at a reduced dose (1, 3, 4) ‣ Can be co-administered with acid- reducing agents (including PPIs) (3, 5) ‣ No dose modification needed for patients with renal impairment or mild-moderate hepatic impairment. ‣ Can be used for patients with severe hepatic impairment at a reduced dose


 
33 2019 3 submissions ‣ MCL and CLL in CN ‣ MCL – US approval 33 2020 22 submissions ‣ 15 for MCL – CN approval ‣ 7 for WM ‣ 1 for CLL – CN approval 2021 40+ submissions planned 9-12 expected approvals ‣ 22 for MCL – 4 approvals (CA, AE, IL, CL) ‣ 13 for WM – 2 approvals (CA, CN) ‣ 8 for MZL ‣ 3 for CLL *EU = 27 countries GLOBAL FOOTPRINT CONTINUES TO EXPAND TO 70+ COUNTRIES*


 
34 BGB-11417 (BCL-2) Source: 1. Hu N et al. Presented at AACR 2021. Abstract 3077. ‣ Better selectivity and more potent than venetoclax, potentially translating to deeper target inhibition and better safety ‣ Potential to overcome resistance to venetoclax (G101V mutant) ‣ A key molecule in heme portfolio ‣ Monotherapy or in combination with zanubrutinib for CLL/NHL ‣ Potential new entry to AML/MDS/MM space Venetoclax BGB-11417 Highly Potent Protein BGB-11417 IC50 (nM) Venetoclax IC50 (nM) Bcl-2 0.014 ± 0.0021 0.20 ± 0.015 Bcl-2- G101V 0.59 ± 0.08 34 ± 3.8 Highly Selective (Inhibition Relative to BCL-2) AN INVESTIGATIONAL BCL-2 INHIBITOR WITH POTENTIAL BEST-IN-CLASS PROPERTIES


 
35Source: 1. Hu N et al. Presented at AACR 2021. Abstract 3077. ‣ Dose escalation ongoing for monotherapy, combination with zanubrutinib, and combination with azacitidine ‣ Clinical activity observed at the first dose level 40 mg ‣ Currently at 320 mg dose level, PK exposure at 80 mg equivalent to that of venetoclax at 400 mg, its approved dose for CLL ‣ Pivotal studies expected to be initiated in 2022 DLBCL FL/MZL MCL CLL AML/MDS MM WM Transformed NHL Phase 1 BGB-11417 mono Phase 1 BGB-11417 mono Phase 1 BGB-11417 ± Zanu Phase 2 in Post BTKi MCL BGB-11417 mono Phase 1 BGB-11417 ± Zanu Phase 2 in Post BTKi CLL/SLL BGB-11417 mono Phase 1b BGB-11417 ± Azacitidine Phase 1b BGB-11417 + Dex or BGB-11417 + Carflizomib + Dex Phase 1 BGB-11417 mono Phase 1 BGB-11417 mono Phase 1 BGB-11417 mono Phase 1 BGB-11417 mono R/R R/R R/R R/R R/R,TN Phase 1 BGB-11417 mono Phase 1 BGB-11417 mono R/R Ongoing Planned R/R R/R R/R R/R,TN R/R R/R R/R R/R BCL-2 PROGRAM CLINICAL PROGRESS UPDATE


 
36 ZANUBRUTINIB, OUR BEST-IN-CLASS BTK INHIBITOR, IS THE CORNERSTONE MOLECULE FOR TREATING B CELL MALIGNANCIES ‣ More efficacious in ALPINE, safer in ALPINE and ASPEN, and more convenient than ibrutinib in clinic ‣ Great combination opportunities with Bcl-2, PI3-Kδ, Revlimid, etc. ‣ Additional new molecules in the pipeline ‣ BTK-CDAC to overcome resistance ‣ CAR-NK, bispecifics, ADC, etc. Growing AML/MDS portfolio ‣ Our investigational Bcl-2 inhibitor, BGB-11417, has better pharmacological properties than venetoclax, similar story as ZANUBRUTINIB ‣ Interesting new molecules targeting CD70, TIM3, CD33, FLT3, & MCL-1


 
37 Yong (Ben) Ben, M.D. CMO, I/O SOLID TUMOR CLINICAL PROGRAM UPDATE


 
38 SUMMARY OF SOLID-TUMOR CLINICAL PORTFOLIO Marketed Products Growing Late- stage Portfolio Robust & Diversified Early Pipeline Zanidatamab HER2 Sotorasib KRAS G12C Sitravatinib multi-target TKI Ociperlimab TIGIT Antibodies OX-40, TIM-3, Bi-specifics Small Molecules HPK-1, RAF Dimer, BCL-2, PI3Kδ Antibody-Drug Conjugates ZW49 >10 molecules with Amgen Global Rights Regional Rights Tislelizumab Pamiparib Note: All marketed products are in China. The NMPA has suspended the importation, sales and use of Abraxane in China.


 
39 DIFFERENTIATED PD-1 ANTIBODY WITH ENGINEERED FC TO AVOID ADCP Nivo/Pembro with FcγRI-binding FcγRI- + Nivolumab Pembrolizumab CD8+ T cell CD4+ T cell - Tislelizumab FcγRI + Macrophage, Monocyte, MDSC, Dendritic cell Tislelizumab without FcγRI-binding ORR CR mPFS Camrelizumab 76.0% (95%Cl: 64.7-85.1) 26.7% 22.5m (95%Cl: 14.7-NR) Sintilimab 85.4% (95%Cl: 76.7-91.8) 29.2% 18.6m (95%Cl: 14.4-22.3) Tislelizumab for cHL Patients Competitor Data for Trials with Similar Patient Population Median PFS: 31.5 months (95% CI: 16.53, NE) (95%CI: 54.9-77.9) 67.1% PR 20% ORR 87.1% (95%CI: 77.0-93.9) Long-term results including safety data were presented at EHA 2021: 1. Song Y et al. Abstract S207. Tislelizumab Cross trial comparison; competitor data from EHA Library. Wu J. 06/09/21; 324614; S206 / Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 7533-7533 / Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 8034-8034.


 
40 Approval On-going Head and neck cancer MSI-H or dMMR tumors Kidney cancer Bladder cancer Hodgkin’s lymphoma Liver cancer Esophagus cancer Gastric cancer Lung cancer Melanoma Merkel cell carcinoma ‣ Approved: 1L non-sq NSCLC, 1L sq-NSCLC, 2/3L HCC, 2/3L UBC and R/R cHL ‣ Under review: 1L NPC, 2/3L NSCLC, 2L ESCC and 2/3L MSI-High 5 Approvals and 4 sBLAs under Review in China ‣ 7 as monotherapy or in combo with SOC expected to readout in next 36 months ‣ 4 combination registration trials ongoing/planned to be initiated with ociperlimab, zanidatamab or sitravatinib 11 Additional Registrational Trials On-going/Planned ‣ 5,300+ pts treated with tislelizumab on BeiGene clinical trials, 1,700+ pts from ex- mainland China ‣ Collaboration with Boehringer Ingelheim, one of the world’s leading biologics manufacturers Global Program Positioned for Global Access ‣ For N. America, Europe and Japan filing and marketing opportunities ‣ Explore therapeutic potential of tislelizumab in combination strategies Collaboration with Novartis CLINICAL DEVELOPMENT PROGRAM Tislelizumab


 
41 STRONG SOLID TUMOR PORTFOLIO CENTERED AROUND PD-1 Activate T cell via stimulation agonists OX40, bispecific T cell engager Overcome PD-1 Ab resistance via TME re-modeling Sitravatinib, TIM3, PI3Kδ, DKK1 Sensitize tumors to PD-1 Ab via immunogenic cell death Zanidatamab, ZW49 Enhance PD-1 response via releasing other immune checkpoint inhibition TIGIT, HPK1


 
42 OCIPERLIMAB (TIGIT) ‣ Positioned to be combined with tislelizumab in PD-1 sensitive tumors ‣ Mechanistically synergize with PD-1 ‣ Highly potent, with intact Fc function ‣ Fc function shown to be critical to activity preclinically ‣ One of the most advanced anti-TIGIT antibodies ‣ 200+ pts have been dosed with oci/tisle combination ‣ Early efficacy observed ‣ Generally well-tolerated, no additional safety signals detected ‣ Two Phase 3s initiated earlier this year, broad clinical programs ongoing Phase 3 Molecules Company # of On-going Ph3 Trials Fc Function Phase 3 Indications Tiragolumab Roche 5 Intact NSCLC; ES- SCLC; ESCC Ociperlimab BeiGene 2 Intact NSCLC Vibostolimab Merck 1 Intact NSCLC Domvanalimab Arcus/ (Gilead) 1 Null NSCLC MoA Source: 1. Frentzas S et al. Presented at: ASCO 2021. Abstract 2583. AUGMENTING PD-1’S ANTI-TUMOR ACTIVITY IN PD-1 SENSITIVE TUMORS


 
43 OCIPERLIMAB (TIGIT) Phase 1a Phase 1b Phase 2 Phase 3 Untreated, locally advanced, unresectable NSCLC AdvanTIG-301, Ociperlimab + Tislelizumab + CRT 1L PD-L1+ NSCLC AdvanTIG-302, Ociperlimab + Tislelizumab 1L All-Comer NSCLC AdvanTIG-205, Ociperlimab + Tislelizumab + Chemo (planned 2H 2021) 1L LS-SCLC AdvanTIG-204, Ociperlimab + Tislelizumab + CRT 2/3L CC AdvanTIG-202, Ociperlimab + Tislelizumab 2/3L ESCC AdvanTIG-203, Ociperlimab + Tislelizumab 1L HCC AdvanTIG-206, Ociperlimab + Tislelizumab + bevacizumab biosimilar NSCLC (sq, non-sq, PD-L1+, CPI), ES-SCLC, ESCC, EAC, HNC, GC BGB-900-105, Ociperlimab +Tislelizumab + chemo Global Global Global Global Global Global Global China CURRENT CLINICAL DEVELOPMENT PROGRAM


 
44 Clinical Development Plan In collaboration with Mirati for Asia (ex-Japan), Australia and New Zealand Phase 1a Phase 1b Phase 2 Phase 3 Sq. & Non-sq. NSCLC, RCC, OC, Melanoma BGB-900-103, +Tislelizumab HCC, GC BGB-900-104, +Tislelizumab Sq. & Non-sq. NSCLC BGB-A317-sitravatinib-301, +Tislelizumab Source: 1. Mirati. 2. He K et al. Presented at SITC 2018. Abstract P385. 3. Msaouel P et al. Presented at SITC 2019. Abstract O23. 4. Cui C et al. Presented at: AACR 2021. Abstract CT035. 5. Goh J et al. Presented at: AACR 2021. Abstract CT013. Mirati conducting other studies, including the Phase 3 SAPPHIRE study in NSCLC SITRAVATINIB REVERSE PD-1 RESISTANCE BY CHANGING TUMOR MICROENVIRONMENT ‣ A potent inhibitor of VEGFR and tumor-associated macrophage (TAM) family kinases (Axl, Tyro3, & Mer) to reverse immune resistance ‣ Inhibit TAM activities (polarization and efferocytosis) that appear to be critical in establishment of an immuno- tolerant state ‣ Block angiogenesis ‣ Clinical activity in combination with PD-1 ‣ OS in PD-1 failed NSCLC: 15.6 months ‣ ORR in PD-1 failed bladder cancer: 27.3% ‣ ORR in PD-1 failed melanoma: 24.0% ‣ ORR in immune-cold PROC: 26.4% ‣ Pivotal studies in NSCLC initiated


 
45 NSCLC Tislelizumab Ociperlimab Sitravatinib Neoadjuvant/ Adjuvant Tisle (PD-1) + Chemo RATIONALE-315 Untreated, Locally Advanced, Unresectable Oci (TIGIT) + Tisle + CRT AdvanTIG-301 1st Line Tisle (PD-1) + Chemo (SQ) RATIONALE-307 Tisle (PD-1) + Chemo (Non-SQ) RATIONALE-304 Oci (TIGIT) + Tisle (PD- L1+) AdvanTIG-302 2nd or 3rd Line Tisle (PD-1 naïve) RATIONALE-303 Sitra + Tisle (PD-1 R/R) BGB-A317-sitravatinib-301 On-going Approval Filing Filings and approvals listed are in China SQ, Squamous Non-small Cell Lung Cancer; Non-SQ, None Squamous Non-small Cell Lung Cancer; CRT, Concurrent Radiochemotherapy BROAD REGISTRATION PROGRAMS IN NSCLC


 
46 In collaboration with Zymeworks for Asia (ex-Japan), Australia and New Zealand ‣ Target two distinct HER2 epitopes, ECD2 (trastuzumab binding domain) and ECD4 (pertuzumab binding domain) ‣ Increased tumor cell binding and enhanced HER2 internalization compared with trastuzumab ‣ Superior to trastuzumab and pertuzumab in preclinical studies ‣ Encouraging anti-tumor activity as monotherapy across multiple HER2-expressing tumor types ‣ 33% ORR in heavily-pretreated HER2 breast cancer ‣ 33% ORR in late-line HER2 gastric cancer ‣ 40% ORR in refractory HER2 biliary tract cancer ‣ Pivotal studies ongoing/planned ‣ Phase 2 single arm study in 2L+ BTC initiated Oct 2020 ‣ Phase 3 in 1L GC planned to be initiated in H2 2021 ZANIDATAMAB (ZW25) Clinical Development Plan Phase 1a Phase 1b Phase 2 Phase 3 BC,GEA,OC BTC,CRC ZWI-ZW25-101, ± Chemo GC ZWI-ZW25-201, + Chemo BC ZW1-ZW25-202, + Palbociclib, Fulvestrant BTC ZWI-ZW25-203, Mono GC ZWI-ZW25-301, + Chemo, Tislelizumab GC, BC BGB-A317-ZW25-101, + Chemo, Tislelizumab (to be initiated) Source: 1. Weisser N et al. Presented at AACR 2021. Abstract 1005 HER2XHER2 BISPECIFIC HER2 ANTIBODY TARGETING HER2 EXPRESSING TUMORS


 
47 BGB-445 is a non-ligand-blocking OX40 Ab which retains OX-40L signal on APC cells and maximizes T cell activation BGB-445 (OX-40) Other OX40 antibodies in clinic are ligand-blocking, which lose OX-40L signal in APC cells ‣ Distinguished MOA vs. other OX-40 antibodies in the clinic ‣ Non-ligand blocking to retain OX-40 ligand signaling in APC cells ‣ Maximize OX-40 signaling in T cells ‣ Clinical progress ‣ Dose escalation on-going as monotherapy and in combination with tislelizumab ‣ No DLT to date ‣ Clinical activity observed in both monotherapy and combination-therapy cohorts ‣ Plan to start dose expansion/Phase 2 later this year or early next year OX-40 Maximum T cell activation Maintain OX-40L signal in APC cells T cell activation Lose OX-40L signal in APC cells OX-40 OX-40L OX-40L Source: Internal data. UNIQUE OX-40 AGONIST ANTIBODY THAT DOES NOT BLOCK LIGAND-BINDING


 
48 ‣ Positioned to be combined with tislelizumab in PD-1 sensitive tumors ‣ HPK1, an intracellular immune checkpoint to negatively regulate T cell activity ‣ Based on MOA, HPK1 inhibitor will synergize with anti-PD-1 antibody ‣ HPK1 is a hard-to-hit target ‣ Challenging to achieve good potency and selectivity due to very low ATP Km ‣ BGB-15025 has good pharmacological properties ‣ Good kinome selectivity ‣ Robust anti-tumor efficacy ‣ Well-tolerated in animal studies ‣ Clinical progress ‣ Phase 1 dose escalation on-going BGB-15025 (HPK1) Efficacious when Combined with PD-1 Inhibitor in Animal Models Treatment DaysM ea n Tu m or V ol um e (m m 3 ±S EM ) 0 5 10 15 20 25 0 500 1000 1500 BGB-15025 Vehicle PD-1 Ab BGB-15025 + PD-1 Ab ** ** MoA Source: Internal data. ** p < 0.01 POTENTIAL FIRST-IN-CLASS HPK1 INHIBITOR


 
49 DEEP SOLID-TUMOR PORTFOLIO Broad global clinical development programs built around tislelizumab, a differentiated PD-1 antibody Multiple combination strategies to enhance response and overcome resistance New assets entering late stage & new wave of molecules planned in the next section


 
50 Lai Wang, Ph.D. Global Head of R&D NEW MODALITIES AND PLANNED PIPELINE


 
51 ENHANCE THE NEXT WAVE OF DRUG DISCOVERY BY INVESTING IN NEW MODALITIES Traditional Small Molecule Monoclonal Ab 2011-2020


 
52 2021 and Beyond Drug Discovery CDAC ADC Pro-Cytokine Cell Therapy BsAb/ TsAb Monoclonal Ab Traditional Small Molecule ENHANCE THE NEXT WAVE OF DRUG DISCOVERY BY INVESTING IN NEW MODALITIES CDAC, Chimeric Degradation Activating Compound; ADC, Antibody Drug Conjugate; BsAb, Bispecific Antibody; TsAb, Trispecific Antibody Power of New Platforms ‣ Drugging the undruggable ‣ Precise tumor targeting


 
53 Drug Discovery CDAC ADC Pro-Cytokine Cell Therapy BsAb/ TsAb Monoclonal Ab Traditional Small Molecule CDAC, Chimeric Degradation Activating Compound; ADC, Antibody Drug Conjugate; BsAb, Bispecific Antibody; TsAb, Trispecific Antibody Power of New Platforms ‣ Drugging the undruggable ‣ Precise tumor targeting


 
54 Differentiated from traditional small molecules by inducing target degradation ‣ Ability to target proteins with or without enzymatic activity ‣ Does not require strong and sustained target binding ‣ Eliminate the scaffolding function of the target MoA Advantage CDAC Degradation via proteosome Linker E3 binder Target binder Ub E3 ligase E2 Protein target Protein target Ub Ub Ub CDAC DRUGGING THE UNDRUGGABLE CHIMERIC DEGRADATION ACTIVATING COMPOUND (CDAC) PLATFORM


 
55 Build strong capability to leverage a wider spectrum of E3 ligases: ubiquitous and tissue specific ‣ Reduce dose-limiting toxicities ‣ Overcome E3-relevant drug resistance ‣ Broaden substrate spectrum Ubiquitous Selective Restricted MDM2 CRBN Ligase A Ligase B VHL Ligase C Ligase D Ligase E Tumor Selective Target DegradationNormal Tissue Expression of Selected E3 Ligases + Normal Cell Tumor Cell Cell Death Unaffected No E3 Expression No Target Degradation CDAC E3 ligase Target protein E3 Expression Target Degradation CDACOUR DIFFERENTIATION


 
56Heme, hematological malignancies; I-O, Immuno-oncology BCR Signaling BTK CDAC to target BTK scaffolding function Receptor Tyrosine Kinase CDAC A to treat lung cancer Cell Cycle CDAC B applicable in heme Apoptosis CDAC C applicable in heme and solid tumors TLR signaling CDAC D applicable in heme and I-O therapies Cytokine signaling CDAC E applicable in heme and I-O therapies Transcription/ epi-genetics CDAC F applicable in heme CDACBROAD CDAC PROGRAMS


 
57 ‣ Next generation BTK inhibitor to enhance BTK franchise ‣ To overcome zanubrutinib and other BTKi resistance ‣ To destroy non-kinase (scaffolding) function ‣ BGB-16673, BeiGene’s first CDAC molecule planned for clinic ‣ Good pharmacological properties ‣ Highly potent and selective ‣ Good oral bioavailability ‣ Long t1/2 ‣ Well-tolerated in animal studies ‣ First patient expected to be dosed in 2H2021 0 5 10 15 20 25 0 500 1000 1500 2000 Treatment Days Tu m or V ol um e (m m 3 ) Vehicle BGB-16673 Zanubrutinib C481S Tumor Model BGB-16673 Can Overcome C481S Resistance CDACBTK CDAC PROGRAM FOR B CELL MALIGNANCES


 
58 Drug Discovery CDAC ADC Pro-Cytokine Cell Therapy BsAb/ TsAb Monoclonal Ab Traditional Small Molecule CDAC, Chimeric Degradation Activating Compound; ADC, Antibody Drug Conjugate; BsAb, Bispecific Antibody; TsAb, Trispecific Antibody Power of New Platforms ‣ Drugging the undruggable ‣ Precise tumor targeting


 
59 TUMOR SELECTIVE TARGETING APPROACH Tumor Associated Antigen (TAA) Toolbox 10+ TAAs are being developed, many associated with multiple tumor types Tumor Selective Immune Cell Activation ‣ Bi/Tri-specific TAA-Immune cell engager ‣ CAR-NK ‣ Immune stimulating-ADC Tumor Targeted Cell Killing ‣ Toxin delivering-ADC Inactive Pro-Cytokine Tumor Selective Cytokine Release Breast Cancer (10 TAAs) Colon Cancer (5 TAAs) Gastric Cancer (6 TAAs) Lung Cancer (11 TAAs) Esophageal Cancer (5 TAAs) Lymphoma (2 TAAs) Leukemia (1 TAAs) Kidney Cancer (2 TAAs) Ovarian Cancer (8 TAAs) Liver Cancer (1 TAAs)


 
60 B ACTIVATING INTRA-TUMOR IMMUNE CELLS BsAb/TsAb Tumor Selective Immune Cell Activation via TAA-oriented Engagement of T/NK Receptors Llama SdAb platform Small Ab unit to be easily used in diverse formats Human SdAb phage library Bypass humanization Common light chain platform IgG-like w/o additional engineering on Fab ScFv engineering platform Convert Fab to good-behave ScFv Comprehensive BsAb/TsAb Discovery Platforms to Fulfil Diverse Formats and MoAs NK cell engager ‣ CD16 T cell engager ‣ CD3 ‣ 4-1BB TAA-targeting ‣ Mono-specific or dual targeting BsAb/TsAb Anti-TAA Anti-immune cell activation receptor SdAb, Single domain Antibody


 
61 OFF-THE-SHELF TUMOR TARGETING NK CELLS Cell Therapy iPSC, Induced pluripotent stem cells iPSC differentiation NK function enhancement Unique CAR platforms GMP capability readiness ScFv generation IND-enabling studies Global clinical development & commercialization CollaborationMoA of CAR-NK iPSC Positioning • Shoreline Biosciences collaboration: fast-track first wave products to development • Internal capability build-up: enable Shoreline Biosciences collaboration and pipeline expansion Planned Portfolio • Start with iPSC-derived, allogeneic CAR-NK cell therapies • Expand therapeutic cell types and utilities as appropriate Tumor Cell CAR CAR-NK Cell Perforin Granzymes Cell Death TAA


 
62 ADCTAA DIRECTED MISSILE 62 DAR, Drug Antibody Ratio NEXT GENERATION ADC designed to have superior efficacy and safety ‣ Site specific conjugation via Ambrx technology to achieve homogeneous drug antibody ratio (DAR) ‣ Innovative linker design to improve ADC biophysical property and stability, and to enhance tumor- selective cleavage Anti-TAA Antibody Payload Toxin-based ADC as Targeted Bomb Immune-Stimulating Antibody Conjugate (ISAC) Tumor cell Cell death Toxin ‣ Tumor-targeted delivery of immune agonists to turn COLD tumors HOT Tumor cell APC (Mφ/DC) Immune activation Immune agonist (TLR7/8, STING) TAA, Tumor Associated Antigen


 
63 TUMOR SELECTIVE CYTOKINE ACTIVATION Scientific rationale ‣ Cytokine therapy to activate the immune system has been an attractive treatment modality in clinical cancer research ‣ Severe systemic toxicity hinders the broad application of immune-stimulating cytokines BeiGene’s pro-cytokine design for tumor-specific cytokine-mediated immune cell activation with minimized peripheral adverse events ‣ Complete masking in circulation ‣ Full recovery of cytokine activity once cleaved ‣ Prolonged half life of the pro-cytokine form ‣ Plug-and-play format applicable to broad cytokine spectrum 63 Cytokine activity blocked by masking moiety attached via a cleavable linker Circulation 1 Inactive form Bulk tumor Immune cell activation by cytokine Linker cleaved by tumor- selective proteases 3 2 Active cytokine released MoA of pro-cytokine Pro-cytokine


 
64 Modality CDAC, Chimeric Degradation Activating Compound; ADC, Antibody Drug Conjugate; BsAb, Bispecific Antibody; TsAb, Trispecific Antibody ‣ 50+ programs ongoing, close to half with first-in-class potential ‣ 10+ planned to clinic in the next 24 months ‣ Going beyond oncology ‣ First immunology/inflammation asset planned to enter clinic later this year ‣ BeiGene institute to focus on early technology and translational science N um be r of P ro gr am s More plannedPro- cytokine CAR-NKADC BsAb/ TsAb CDAC Traditional SM mAb PRECLINICAL PIPELINE


 
65 Stroma Stroma cell depletion Novel target H (mAb) Treg cell depletion Novel target E (mAb) Treg cell inhibition Novel target A (SM) DC expansion and activation Novel target F, G (recombinant protein) Novel target B (CDAC) Checkpoint blockade Novel target I, J (mAb) Novel target C, D (SM) Cytokine Pro-cytokine K Checkpoint blockade Novel target I, J (mAb) Novel target C, D (SM) Cytokine Pro-cytokine K Treg Cell Cytotoxic T Cell DC NK Cell MDSC Macrophage activation and re- polarization Novel target A (SM) Biologics Small Molecule (SM) Sitravatinib (TAM) PI3Kδ DKK1 Sitravatinib PI3Kδ OX40 TIGIT TIM-3 OX40 TIGIT TIM-3 PD-1/L1 OX-40 TIM-3 TIGIT FAP-4-1BB HPK1 PD-1/L1-IL21 Sitravatinib (VEGFR)Lenalidomide CANCER-ATTACKING IMMUNE MODULATING STRATEGIES TAA DRIVEN THERAPEUTICS NOT INCLUDED Graph adapted from Daniel S. Chen, Immunity, 2013 CDAC Pro-cytokine SM, mAb


 
66 ONLY THE BEGINNING Productive first decade establishes scientific track record ‣ Zanubrutinib and tislelizumab – set stage for leading franchises ‣ Deep portfolio built around these cornerstone assets – many moving into pivotal stage BeiGene’s R&D model stands to deliver significant innovation in the next decade ‣ Discovery engine has flourished and diversified ‣ Clinical pipeline expected to accelerate ‣ Poised to develop novel, science-based combinations ‣ Unique clinical development model and truly global, in- house capabilities at scale, speed and cost advantages


 
67 CLOSING REMARKS


 
68 OUR TRUE NORTH IS PATIENTS Continued innovation and expansive growth planned in next 10 years Amazing research across number of platforms with scale and talent 1 Future innovation requires deep portfolio with breadth of modalities (combinations) 2 One of the largest research organizations with executional and cost focus 3 Speed, cost advantage to accelerate combination strategy4


 
69 Angus Grant, Ph.D. Chief Business Executive Julia Wang Chief Financial Officer Q&A PARTICIPANTS Xiaodong Wang, Ph.D. Chairman of Scientific Advisory Board & Co-Founder William Novotny, M.D. Head of Clinical Development, Hematology Yong (Ben) Ben, M.D. Chief Medical Officer, Immuno-Oncology John V. Oyler Co-founder, Chairman and CEO Xiaobin Wu, Ph.D. President, Chief Operating Officer Lai Wang, Ph.D. Global Head of R&D Josh Neiman Chief Commercial Officer, North America and Europe


 
70 THANK YOU


 
71 ABBREVIATIONS Ab Antibody Acala Acalabrutinib ADC Antibody drug conjugate ADCP Antibody-dependent cellular phagocytosis AE Adverse Event AE/UAE United Arab Emirates AFIB Atrial fibrillation ALL Acute lymphocytic leukemia ALT Alanine aminotransferase AML Acute myeloid leukemia ANZ Australia and New Zealand APAC Asia Pacific APC Antigen-presenting cells APC Acute pancreatic cancer AST Aspartate aminotransferase BC Breast cancer BCL-2 B-cell lymphoma-2 BCRP Breast cancer resistance protein BI Boehringer Ingelheim BIC Bayesian Information Criterion BIC Best-in-Class BID Twice a Day BLA Biologics License Application BMS Bristol Myers Squibb BR Bendamustine and Rituximab BsAb Bispecific Antibody BTC Biliary tract cancer BTK Bruton's Tyrosine Kinase BTK-CDAC Bruton tyrosine kinase-Chimeric Degradation Activating Compound CA California CA Canada CAR Chimeric antigen receptor CAR-NK Chimeric antigen receptor-Natural Killer cell CC/CRC Colorectal Cancer CCRCC Clear cell renal cell carcinoma CDAC Chimeric Degradation Activating Compound Chemo Chemotherapy cHL Classical Hodgkin’s Lymphoma CHO Chinese hamster ovary CI Confidence interval CL Chile CLD Chronic liver disease CLL Chronic lymphocytic leukemia CMC Chemistry, Manufacturing and Controls CN China COVID-19 Coronavirus disease 2019 CR Complete Response CRBN Cereblon CRO Contract Research Organization CRT Conformal Radiation Therapy CRT Concurrent Radiochemotherapy CT Computed tomography CTC Circulating tumor cell CTL Cutaneous T-cell lymphoma DAR Drug to antibody ratio DC Discontinuation from study treatment DCP Decision Check Point DDI Drug-drug interaction del(17p) Deletion of 17p


 
72 ABBREVIATIONS (CONT’D) DKK1 Dickkopf-1 DLBCL Diffuse large B-cell lymphoma DLT Dose limiting toxicity dMMR Deficient Mismatch Repair DOR Duration of Response EAC Esophageal adenocarcinoma ECD2 Extracellular domain 2 ECD4 Extracellular domain 4 EHA European Hematology Association EMEA European Medicines Evaluation Agency EMEA Europe Middle East Africa Er+ Oestrogen receptor positive ESCC Esophageal Squamous-Cell Carcinoma ES-SCLC Extensive-stage small cell lung cancer EU European Union Fab Fragment of antigen binding FCR treatment Fludarabine, cyclophosphamide and rituximab treatment FcγR Fcγ receptor FDA US Food and Drug Administration FIC Fractional inhibitory concentration FIC First-in-Class FIH First-in-human FL Follicular lymphoma GBM Glioblastoma gBRCAm Germline Breast Cancer mutation GC Gastric cancer GC/GRJC Gastric cancer/Gastroesophageal Junction Cancer GCTB Giant cell tumor of bone GEA Gastroesophageal Adenocarcinoma GMP Good Manufacturing Practice HC Headcount HCC Hepatocellular Carcinoma Heme Hematological malignancies HER2 Human Epidermal Growth Factor Receptor 2 HL Hepatic lipase HL Hodgkin lymphoma HLE BiTE Half-life extended Bi-specific T-cell engagers HNC Head and neck cancer HNSCC Head and Neck Squamous Cell Carcinoma HPK-1 Hematopoietic progenitor kinase 1 HR Hazard ratio HRD Homologous recombination deficiencies HTH Head to Head HTS High-throughput sequencing I/I Immunology/Inflammation IgG-like BsAb IgG-like bispecific antibodies IGHV Immunoglobulin heavy chain variable region IL Israel IL Interleukin IND Investigational new drug I-O Immuno-oncology IPD Integrated Product Development iPSC Induced pluripotent stem cells IRC Independent Review Committee ISAC Immune Stimulating Antibody Conjugate ISR Incurred sample reanalysis JP Japan KOL Key Opinion Leader KRAS Kirsten Rat Sarcoma Viral Oncogene Homolog LN Lupus Nephritis


 
73 ABBREVIATIONS (CONT’D) MA Massachusetts mAb Monoclonal Antibody MCL Mantel Cell Lymphoma Mcl-1 Myeloid cell leukemia 1 mCRPC Metastatic Castration-Resistant Prostate Cancer MDM2 gene Murine double minute 2 gene MDS Myelodysplastic syndromes MDSC Myeloid-derived suppressor cell MEL Melanoma MM Multiple Myeloma MoA Mechanism of Action mPFS Median Progression-free survival Mpfs Progression-free survival duration in months MPN Myeloproliferative neoplasm MRD Minimal Residual Disease MRI Magnetic resonance imaging mRNA Messenger RNA MRR (CR+VGPR+PR) Major response rate MSI-H Microsatellite Instability High MZL Marginal zone lymphoma Mφ/DC Macrophages (MΦ) /dendritic cells (DC) N/SCLC Non-/small cell lung cancer NA Not applicable NALA North America Latin America NCT National Clinical Trial Network NDA New Drug Application NE Not Evaluable NHL Non-Hodgkin’s lymphoma NJ New Jersey NK cell Natural killer cells NMPA National Medical Products Administration Non-sq. NSCLC Non-squamous non-small cell lung cancer NPC Nasopharyngeal carcinoma NR Not reached N-RAS Neuroblastoma RAS Viral Oncogene Homolog NRDL National Reimbursement Drug List NSCLC Non-small-cell lung cancer Obin Obinutuzumab OC Ovarian Cancer oci Ociperlimab ORR Overall Response Rate OS Overall Survival OX-40 Ab OX-40 Antibody OX-40 L OX-40 Ligand PARP Poly ADP-Ribose Polymerase Pca Prostate Cancer PD Disease Progression PD-1 Programmed Cell Death protein 1 PD-L1 Programmed Cell Death Ligand 1 Pembro Pembrolizumab PFS Progression-Free Survival P-Gp P-glycoprotein PI3Kδ Phosphoinositide 3-kinase delta PO Oral PPI Proton Pump Inhibitor PR Partial Response PROC Platinum-resistant Ovarian Cancer PSOC Platinum-sensitive Ovarian Cancer pt Patient


 
74 ABBREVIATIONS (CONT’D) QD Once a Day R&D Research and Development R/R Relapsed / Refractory R/R cHL Relapsed/refractory Classical Hodgkin Lymphoma RCC Renal Cell Carcinoma RP2D Recommended Phase 2 Dose sBLA Supplemental Biologics License Application ScFv Single-Chain Fragment Variable SCLC Small Cell Lung Cancer SD Stable Disease SEC Securities and Exchange Commission Sitra Sitravatinib SK South Korea SLL Small Lymphocytic Lymphoma SM Small Molecule SOC Standard of Care SPD Solution Program Development Sq. NSCLC Squamous Non-small Cell Lung Cancer SVP Subvirus Particle TAA Tumor associated antigen TAM Tamoxifen TCR T cell receptor TIGIT T cell immunoreceptor with Ig and ITIM domain TIM-3 T-cell immunoglobulin and mucin-domain containing-3 Tisle Tislelizumab TKI Tyrosine kinase inhibitor TLR Toll-like receptor TME Tumor Microenvironment TN Treatment-naïve TPD Technology Platform Development TR Technical Review TsAb Trispecific Antibody TTR Time to response Ub Ubiquitin UBC Urinary bladder cancer UC Urothelial carcinoma US United States VEGF Antivascular endothelial growth factor VEGFR Vascular endothelial growth factor receptor VGPR Very Good Partial Response w/o without WM Waldenström’s Macroglobulinemia YTD Year to Date