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 products; the conduct of late-stage clinical trials and expected data readouts; additional planned commercial product launches; the advancement of and anticipated clinical development, regulatory milestones and commercialization of BeiGene’s products 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 products and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; the impact of the COVID-19 pandemic on the Company’s clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. 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. 1
Key Potential 2021 catalysts • Up to 12 commercial products • Multiple commercial launches and reimbursement opportunities for tislelizumab and BRUKINSA • Key Phase 3 readouts: BRUKINSA CLL • Internal pipeline advancements: ociperlimab (TIGIT), Bcl-2 Global 5,000+ organization • 10 offices on 5 continents • Global clinical development: 1,600+ • Commercial: 1,800+ (China) 100+ (U.S.) • Research: ~500 • Internal manufacturing capabilities 3 Fully-Integrated Global Biotech Company with Unique Strategic Competitive Advantages in Clinical Science and China Commercial 1. November 14, 2019; this indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 2. June 3, 2020 for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least one prior therapy, and for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 3. December 26, 2019; approved for patients with classical Hodgkin’s lymphoma who have received at least two prior therapies. April 10, 2020 for the treatment of patients with previously treated locally advanced or metastatic urothelial carcinoma (bladder cancer). 4. April 20, 2020, June 19, 2020, July 1, 2020, respectively. U.S. launch for R/R MCL1; China launch for R/R MCL, R/R CLL/SLL2 Global strategic collaboration $2.8 billion investment Commercial and pipeline assets tislelizumab R/R cHL & R/R UC launched3, 1L Sq & non-Sq NSCLC sNDAs accepted, 2L/3L HCC sNDA accepted4 + Broad portfolio over 30 assets • 7 approved medicines incl. 1 in U.S. • 15 NDAs accepted for 7 medicines in 4 countries and the EU • 30+ commercial or clinical stage assets, including 10+ with global rights, 20+ with China/APAC rights • 25+ filed or potentially registration- enabling trials ongoing, 60+ studies in total
4 Transformational Collaboration with Amgen Validates BeiGene’s China-inclusive global development and commercial capabilities • Collaboration rationale – Joining forces to fight one common enemy: cancer – Expected to accelerate access to important oncology medicines for patients in China and globally • BeiGene has already or expects to launch three Amgen oncology medicines in China • Companies to jointly develop Amgen oncology pipeline assets – BeiGene to lead development and commercialization in China as well as contribute to funding global development – BeiGene receives royalties on global ex-China sales (excluding sotorasib) and on China sales after commercialization • Investment by Amgen of $2.8B for 20.5% stake of BeiGene • Tony Hooper, former Amgen EVP of Global Commercial Operations, joined the BeiGene board
5 Regulatory Reforms and Reimbursement Expansion in China Create a Historical Opportunity for the Industry Source: 1. Trialtrove; Industry association; 2. BeiGene analysis 0% 5% 10% 15% 20% 25% 30% 0 3 6 9 12 15 18 21 1 2 3 4 5 6 T h o u s a n d s China’s Rising Share in Global Trials1 Series1 Series2 Series3 China Is Now An Integral Part of Industry Development • Increasing share of trials run in China after joining ICH in 2017, bringing China’s large patient pool into global clinical science ecosystem – which has the potential to dramatically accelerate development and reduce costs • Beginning to meaningfully contribute to paying for innovation – MNC oncology product sales in China witnessed a significant uptick as a result of expanded NRDL coverage – AZ 9-month 2020 revenue was $4.0 billion from China, 21% of total global revenue, US was $6.4 billion, 34% of total Future Key Success Factors • Clinical excellence through: – Global, highly China-inclusive clinical trials – Next generation clinical technology approaches • Creation of science/medicine-based commercial capabilities in China • Global business model provides broader access and supports pricing that enables the ROW to contribute to covering the cost of innovation China Trial ShareEx-China TrialsChina Trials 2015 2016 2017 2018 2019 0 500 1000 1500 2000 2500 3000 3500 MNC Oncology Product Sales in China ($M)2 2020 (Q1-3) YoY Growth: 20% 2020
6 Our Strategies for Building a Leading Global Innovative Biotech Company from China Realize two large internally-developed near-term commercial opportunities • BRUKINSA (zanubrutinib) for the global market as a potentially best-in-class BTK inhibitor • Tislelizumab as a uniquely designed PD-1 antibody for the most common cancers in China and Asia Utilize our key strategic capabilities • Research team ~500, proven track record, 11 molecules discovered in-house, advanced to clinic in 10 years • Development team 1,600+ integrated across China/U.S./AU/EU • Commercial platforms in China and the U.S., the two largest pharmaceutical markets Expand our portfolio by leveraging our clinical and commercial capabilities • Capture opportunities created by regulatory reforms in China • Accelerate global development through China-inclusive global trials Pursue a new global model for long-term growth in the industry • Uniquely positioned due to strong China presence and global development capabilities
7 BRUKINSA (Zanubrutinib) Overview Potentially best-in-class BTK inhibitor Sources: 1. ICML 2019 Song et. al.; 2. ASCO 2020 Tam et. al.; 3. Cull et. al. ASH 2019; 4. Tam et. al. ASH 2019; 5. As of January 10, 2021. BTK: Bruton’s tyrosine kinase; CLL/SLL: chronic lymphocytic leukemia/small lymphocytic lymphoma; CR: complete response; FL: follicular lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; MRR: major response rate; NDA: new drug application; ORR: overall response rate; R/R: relapsed/refractory; RT: Richter’s transformation; VGPR: very good partial response; WM: Waldenström’s macroglobulinemia. ADVANTAGES • Second generation, maximize BTK occupancy, minimize off-target binding • Advantageous label in R/R MCL (dose flexibility-QD/BID, 100% BTK occupancy, PPI/H2RA) • Randomized Phase 3 data demonstrated improved safety / tolerability and suggested improved efficacy • Priced more affordably than competitors in U.S. (8.7% v acalabrutinib, 7.4% v ibrutinib) KEY TARGET INDICATIONS Chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma CLINICAL DATA 86-patient R/R MCL1 84% ORR 59% CR 83-patient R/R WM2 94% ORR 28% VGPR 101-patient R/R CLL/SLL3 95% ORR 14% CR 109-patient 1L CLL/SLL Del17p4 93% ORR 2% CR REGULATORY STATUS • U.S. FDA accelerated approval in R/R MCL on November 14, 2019 • NMPA approval in China for R/R MCL and R/R CLL/SLL on June 3, 2020 • Filings accepted: WM: Australia, Canada, China, and EU; MCL: Australia, Israel BREADTH OF PROGRAM • Over 3,1005 subjects enrolled in clinical trials, safety data on over 600 patients in FDA label • Over 25 clinical trials in eight indications • Over 40 presentations of zanubrutinib clinical data • Potential combination with wholly-owned Bcl-2 inhibitor
8 BRUKINSA (Zanubrutinib) Overview Nine filed or potentially registration-enabling studies ^Time of the announcement of the enrollment completion; 1L: First Line; CLL/SLL: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; CR: Complete Response; DLBCL: Diffuse Large B-Cell Lymphoma; FL: Follicular Lymphoma; GCB: Germinal Center B-cell-like; MCL: Mantle Cell Lymphoma; MRD: minimal residual disease; MRR: Major Response Rate; MZL: Marginal Zone Lymphoma; NHL: Non-Hodgkin’s Lymphoma; ORR: Overall Response Rate; PCNSL: Primary Central Nervous System Lymphoma; PE: Primary endpoint; PFS: Progression-Free Survival; RP2D: Recommended Phase 2 Dose; R/R: Relapsed / Refractory; RT: Richter’s Transformation; VGPR: Very Good Partial Response; WM: Waldenström’s Macroglobulinemia. 1. global trial and potentially registration-enabling in certain countries. Phase 21 (n=65) in R/R MZL (MAGNOLIA), zanu monotherapy, PE: ORR Initiated: Feb 2019, complete^: Mar 2020 Phase 2 (n=41) in R/R non-GCB DLBCL, zanu monotherapy, PE: ORR Initiated: Jun 2017 Phase 3 (n=229) in WM (ASPEN) zanu vs. ibrutinib, PE: VGPR/CR, Filed: multiple geographies Phase 3 (n=550) in 1L CLL/SLL (SEQUOIA) zanu vs. BR, PE: PFS, Initiated: Nov 2017, Enrollment complete^: Aug 2019 Phase 3 (n=600) in R/R CLL/SLL (ALPINE) zanu vs. ibrutinib, PE: ORR Initiated: Nov 2018 Pivotal Phase 2 (n=210) in R/R FL Obinutuzumab ± zanu, PE: ORR Initiated: Nov 2017 Pivotal Phase 2 (n=91) in R/R CLL/SLL zanu monotherapy, PE: ORR Initiated: Mar 2017, Enrollment complete: Dec 2017 Approved by NMPA Jun 2020 Pivotal Phase 2 (n=86) in R/R MCL zanu monotherapy, PE: ORR Initiated: Mar 2017, Enrollment complete: Sep 2017 Approved by U.S. FDA in Nov 2019 under accelerated approval, approved by NMPA Jun 2020 Pivotal Phase 2 (n=44) in R/R WM zanu monotherapy, PE: MRR NMPA filing accepted, priority Nov 2020 Phase 3 (n=500) in 1L MCL R+zanu vs. R+chemo, PE: PFS Initiated: Nov 2019 Enrollment complete EnrollingWM FL MZL MCL C L L C o m b in a ti o n D L B C L Planned Filed, in NDA review Phase 1 (n=94) in R/R DLBCL, zanu + lenalidomide ± R, EP: Safety, ORR Initiated: Sep 2020 Phase 1b: zanu + obinutuzumab, R/R CLL Phase 2 (n=77) in 1L CLL/SLL and MCL, zanu + venetoclax + obinutuzumab (BOVen study), EP: MRD undetectable response Initiated: Feb 2019 Phase 1/2 cohort (n=45) in MCL zanu monotherapy, PE: Safety, RP2D Initiated: Aug 2014 Phase 1/2 cohort (n=125) in CLL/SLL zanu monotherapy, PE: Safety RP2D Initiated: Aug 2014 Filed or potentially registrational CLL/ SLL Phase 1b (n=90) in B-cell malignancies, zanu + tislelizumab, PE: Safety, RP2D Initiated: Jun 2016 Phase 1b: zanu + R-chemo, 1L and 2L DLBCL Phase 2 (n=40) in R/R CLL, zanu + venetoclax + obinutuzumab (GCLLSG study), EP: MRD Initiated: Oct 2020 Phase 1b (n=177) in B-cell Malignancies, zanu + ME-401, PE: Safety, minimum biologically effective dose Initiated: Oct 2016 China Global Phase 1/2 (n=80) in WM zanu monotherapy, PE: Safety, RP2D Initiated: Aug 2014 Phase 2 (n=60) in previously treated CLL/SLL (ibrutinib intolerant) zanu monotherapy, PE: Frequency and severity of treatment-emergent AEs of interest Initiated: Nov 2019 Phase 1 (n=116) in B-cell malignancies, Bcl-2 inhibitor BGB-11417 ± zanu, EP: Safety, RP2D Initiated: Mar 2020 Approved Phase 2 (n=42) in COVID-19 zanu monotherapy, 28 day respiratory- failure free survival Initiated: May 2020 COVID -19 B-cell
9 Tislelizumab Overview PD-1 inhibitor developed globally, targeting Asia-prevalent tumors ADVANTAGES • Differentiated mechanism: minimized binding to FcγR • Differentiated Hodgkin’s data with high CR rate; strong clinical data in lung cancer with three Phase 3 trials having read out positively at interim analyses in first- and second-line settings • To enable broad reimbursement, aggressively pursuing label in most common cancers in Asia • World-class manufacturing partner with BI, 35 years of experience, >35 molecules brought to market KEY TARGET INDICATIONS Breadth wins in China’s label-based reimbursement: Lung, liver, gastric, and esophageal cancers, classical Hodgkin’s lymphoma, urothelial carcinoma, nasopharyngeal, MSI-High CLINICAL DATA 360-patient 1L Sq NSCLC1 Tisle+PC mPFS 7.6mo HR 0.52a Tisle+nPC mPFS 7.6mo HR 0.48b PC mPFS 5.5mo 334-patient 1L Nsq NSCLC2 Tisle+PP: mPFS 9.7mo HR 0.65c PP: mPFS 7.6mo 65-patient China label data R/R cHL3 77% ORR 62% CR 101-patient China label 2L+ PD‐L1+ UC4 25% ORR 10% CR REGULATORY STATUS • China NMPA approval of tislelizumab in R/R cHL on December 26, 2019 • China NMPA approval of tislelizumab in R/R PD-L1+ UC on April 10, 2020 • NMPA accepted sNDAs for 1L sq-NSCLC, 1L Non-sq-NSCLC, 2L/3L HCC on April 20, June 19 and July 1, 2020 BREADTH OF PROGRAM • Over 7,7005 subjects enrolled in tislelizumab studies • Over 25 clinical trials in a dozen indications • Over 30 presentations of tislelizumab clinical data Sources: 1. Wang et. al., ASCO 2020; 2. Lu et. al., ESMO 2020; 3. Chinese cHL label; 3. Chinese UC label; 5. As of January 10, 2021. a. p-value=0.0001, b. p-value<0.0001, c. p-value=0.0044. cHL: classical Hodgkin’s lymphoma; CR: complete response; HR: hazard ratio; MSI: microsatellite instability; NDA: new drug application; NMPA: National Medical Products Administration; nPC: nab-paclitaxel; NSCLC: non small cell lung cancer; ORR: overall response rate; PC: paclitaxel; PD-L1: programmed death ligand-1; PP: pemetrexed+platinum (carboplatin or cisplatin); R/R: relapsed/refractory; Sq: squamous; Tisle: tislelizumab; UC: urothelial carcinoma.
10 Tislelizumab Broad Late-stage Development Program Sixteen filed or potentially registration-enabling studies ^Time of the announcement of the enrollment completion; *Tislelizumab dosage 200mg every three weeks, Q3W. Global Ph2 in R/R/ NK/T-cell lymphoma and Ph2 trial in MSI-H or dMMR solid tumors in China are potentially registrational-enabling trials. 1/2L: First/Second Line; cCRT: concurrent chemoradiotherapy; cHL: Classical Hodgkin’s Lymphoma; ESCC: Esophageal Squamous-Cell Carcinoma; GC: Gastric Cancer; HCC: Hepatocellular Carcinoma; IRC: Independent Review Committee; ITT: Intent-to-treat; MSI-H or dMMR: Microsatellite Instability High or Deficient Mismatch Repair; NDA: New Drug Application; NK: Natural Killer; NSCLC: Non-Small Cell Lung Cancer; ORR: Overall response rate; OS: Overall survival; PE: Primary Endpoint; PFS: Progression-free survival; R/R: Relapsed / Refractory; UC: Urothelial Carcinoma; China Enrollment complete Enrolling Planned Filed or potentially registrational Phase 3 (n=800) in 2L NSCLC tislelizumab vs. docetaxel, PE: OS Initiated: Nov 2017, Positive interim analysis Nov 2020 Pivotal Phase 2 (n=70) in R/R cHL tislelizumab monotherapy, PE: ORR Initiated: Apr 2017, Enrollment complete: Nov 2017, NDA accepted in Aug 2018 and approved by NMPA Dec. 2019 Pivotal Phase 2 (n=110) in 2L UC tislelizumab monotherapy, PE: ORR, Initiated: Jul 2017 Enrollment complete: Aug 2018, NDA accepted in May 2019 and approved by NMPA in May 2020 Lung GC HCC Phase 2 (n=225) in 2L/3L HCC tislelizumab monotherapy, PE: ORR by IRC Initiated: Apr 2018, Enrollment complete^: Feb 2019, sNDA accepted Jul 2020 ESCC Phase 3 (n=450) in 2L ESCC tislelizumab vs. single-agent chemo (paclitaxel, docetaxel, or irinotecan), PE: OS Initiated: Jan 2018, Enrollment complete^: 1Q20 Phase 3 (n=720) in 1L advanced GC tislelizumab or placebo + platinum- and fluoropyrimidine- based chemo, Co-PE: PFS and OS Initiated: Dec 2018 Phase 3 (n=320) in 1L Stage IIIB or IV non-squamous NSCLC tislelizumab+ chemo (platinum-pemetrexed) vs. chemo, PE: PFS Initiated: Jul 2018, Enrollment complete^: Aug 2019, sNDA accepted Jun 2020 UC MSI-H or dMMR solid tumors Phase 3 (n=640) in 1L HCC tislelizumab vs. sorafenib, PE: OS Initiated: Jan 2018, Enrollment complete^: Nov 2019 Phase 3 (n=360) in 1L Stage IIIB or IV squamous NSCLC tislelizumab+ paclitaxel and carboplatin combo or nab-paclitaxel and carboplatin combo vs. paclitaxel and carboplatin combo, PE: PFS Enrollment complete^: Aug 2019, sNDA accepted Apr 2020 Phase 3 (n=480) in 1L advanced ESCC tislelizumab or placebo + platinum- and fluoropyrimidine-based chemo, Co- PE: PFS and OS Initiated: Dec 2018 cHL Pivotal Phase 2 (n=60) in MSI-H or dMMR solid tumors tislelizumab monotherapy, PE: ORR Initiated: Sep 2018 Phase 3 (n=256) in 1L tislelizumab + chemo (gemcitabine plus cisplatin) vs. placebo + chemo PE: PFS Initiated: Apr 2019, Enrollment complete^: Nov 2020 NPC Phase 3 (n=450) in 1L UC tislelizumab + chemo (cisplatin + carboplatin + gemcitabine) vs placebo + chemo PE: OS Initiated: June 2019 Phase 3 (n=316) in localized ESCC tislelizumab + chemoradiotherapy vs chemoradiotherapy, PE: OS Initiated: May 2019 Global Phase 3 (n=364) in 1L SCLC Tislelizumab+ chemo (Carbo/Cis-platin, Etoposide) vs. plac+ chemo, PE: PFS, OS Initiated: July 2019 Filed, in NDA review Approved Phase 3 (n=380) Neoadjuvant in Stg II/IIIA NSCLC Tislelizumab+ chemo (Platinum doublet) vs. placebo + chemo, followed by tislelizumab or placebo Initiated: May 2020
16% 9% 55% 17% 3% ABRAXANE REVLIMID VIDAZA tislelizumab BRUKINSA XGEVA $16M $23M $31M $38M $38M $57M $58M $50M* $57M $52M^ $66M $91M 0 20 40 60 80 100 11 Commercial Footprint in Two Largest Pharmaceutical Markets with a Science and Medicine-Based Team 1. As of January 8, 2021; * Sales negatively impacted by temporary supply disruptions of ABRAXANE; ̂Revenues in the first quarter were subject to the negative impact of the COVID-19 pandemic, increased generic competition, and the suspension of ABRAXANE sales in China by the NMPA in March 2020. Marketed brand revenue A growing 1,900+1 top innovative oncology commercial team Xiaobin Wu, Ph.D. GM of China, President Pfizer Wyeth Bayer Anita Wu Chief Commercial Officer, Greater China Sanofi AstraZeneca Lily Liu VP, Head of Marketing, Greater China Takeda Pfizer Josh Neiman Head, U.S. Commercial Flatiron Onyx Pharmaceuticals Genentech 0 300 600 900 1200 1500 3Q 2020 Marketed Products Breakdown (by product revenue)
12 Running Global Trials of the Highest Quality Incorporating China BeiGene trials in over 35 countries & regions • Global clinical development organization of over 1,600+ people across 10 offices and 5 continents • Over 11,000 subjects enrolled by BeiGene • Running 60+ clinical trials in over 35 countries or regions ⎻ 25+ Phase 3 or potentially registration-enabling studies Melika Davis VP, Global Head of Clinical Operations SVP, Global Head of Drug Development Quality at Novartis John Freeman SVP, Chief Safety Officer SVP, Head of Global Drug Safety & Risk Management at Celgene Lai Wang, Ph.D. SVP, Head of Global Research, Clinical Operation & Biometrics and APAC Clinical Development UT Southwestern Medical Center Jane Huang, M.D. Chief Medical Officer， Hematology Genentech, Acerta Yong Ben, M.D. Chief Medical Officer， Immuno-Oncology BioAtla, AstraZeneca
13 Research Delivered 11 Molecules to the Clinic in Its First 10 Years Beijing Research Center (ONLY 1ST AND 2ND FLOOR) • Team size <200 • 6-8 preclinical programs Beijing Research Center Shanghai Research Center • Team size ~500 • ~12 preclinical programs Beijing Research Center Shanghai Research Center • Team size 700+ • ~24 preclinical programs 2011–2018 TODAY NEAR FUTURE
• Future planned capacity >120,000L, can accommodate expansion to >200,000L • Current: 64,000L; Future: Guangzhou expansion >60,000L, US expansion planned • Lyophilization and liquid fill, 10 fill/finish lines, 3 packaging lines, pilot API, dual source BTK API planned 14 Strong Manufacturing Capabilities EXPERIENCED, HIGH-QUALITY MANUFACTURING PARTNERS • Manufacturing collaborations with leading high-quality manufacturers in biologics and small molecules • BI collaboration established in 2013, cell line and CMC process for tislelizumab developed by BI • Catalent 15mm doses, expansion to ~50mm in process • Aligned with the design criteria of U.S., EU, and China • Commercial-scale small molecule drug products facility • Pilot-scale biologic facility Jonathan Liu, Ph.D. SVP, Bio-Manufacturing J&J, Head of China Pharmaceutical Development and Manufacturing Sciences William Novotny, Advisor, Technical Operations BMS, VP and Global Lead in Supply Chain Merck, AVP in Global Supply Chain Management and Product Operations Michael Garvey VP, Head of Guangzhou Biologics Manufacturing Samsung Biologics, VP of Manufacturing Zhengming Du, Ph.D. Head of Chemistry Manufacturing & Control (CMC) Roche China, Head of Process and Synthesis, Deputy Head of CMC MULTI-FUNCTIONAL MANUFACTURING FACILITY IN SUZHOU BIOLOGICS MANUFACTURING FACILITY IN GUANGZHOU
PRODUCT LEAD INDICATIONS MECHANISM OF ACTION REGULATORY STATUS COMMERCIAL RIGHTS 2019 GLOBAL SALES PARTNER R/R MCL (U.S.) / R/R MCL and R/R CLL/SLL (China) BTK inhibitor Approved in the U.S./ Approved in China Global NA N/A R/R classical Hodgkin’s lymphoma / R/R PD-L1+ urothelial carcinoma Anti-PD-1 antibody Approved in China Global NA N/A pamiparib Ovarian, Breast, Prostate Cancers PARP Inhibitor NDA accepted in China Global NA N/A Breast cancer Microtubule inhibitor Approved in China1 Mainland China $1.3B* BMS R/R adult multiple myeloma, newly diagnosed multiple myeloma Direct anti-tumor, anti- angiogenesis, immunomodulation Approved in China Mainland China $10.8B* BMS Myelodysplastic syndromes, acute myeloid leukemia, chronic myelomonocytic leukemia DNA hypomethylation, direct cytotoxicity Approved in China Mainland China $605M* BMS Giant cell tumor of bone / Skeletal Related Events (SREs) Anti-RANK ligand antibody Approved in China Mainland China $1.9B^ Amgen Multiple myeloma Proteasome inhibitor NDA filed in China Mainland China $1.0B^ Amgen Acute lymphocytic leukemia Anti-CD19 x anti-CD3 bispecific (BiTE) antibody Approved in China Mainland China $312M^ Amgen Idiopathic multicentric Castleman disease IL-6 antagonist Fast track listed in China Greater China NA EUSA QARZIBA (dinutuximab beta) High-risk neuroblastoma Anti-GD2 antibody BLA accepted in China Mainland China NA EUSA BAT1706 (Avastin biosimilar) Colorectal, Lung, Liver cancers Anti-VEGF antibody BLA Accepted in China Greater China NA Bio-Thera tislelizumab 15 Growing Commercial-Stage Portfolio 1 As announced previously, the NMPA suspended the importation, sales and use of ABRAXANE® (nanoparticle albumin-bound paclitaxel) in China supplied to BeiGene by Celgene Corporation, a Bristol Myers Squibb (BMS) company. Source: * Celgene, ̂Amgen. MCL = mantle cell lymphoma, CLL/SLL = chronic lymphocytic leukemia/small cell lymphoma.
16 BeiGene’s Internal Pipeline Three late-stage, and eight early-stage clinical assets *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 approvals. † R/R or not suitable for chemo-immunotherapy ASSETS PROGRAMS DOSE ESC. DOSE EXPANSION PIVOTAL FILED MARKET PH1a PH1b PH2* PH2** PH3 zanubrutinib (BTK) monotherapy R/R MCL (Accelerated approval in the U.S. 11.14.19) WM† (MAA accepted 06.18.20), R/R MCL (NDA in Israel accepted 05.21.20) R/R MCL, R/R CLL/SLL (Approved by NMPA in China 06.03.20) R/R WM 1L CLL/SLL, R/R CLL/SLL R/R MZL Previously treated CLL/SLL (ibrutinib intolerant) combination +rituximab 1L MCL +obinutuzumab R/R FL +lenalidomide +/- ritux. R/R DLBCL tislelizumab (PD-1) monotherapy R/R cHL (approved 12.26.19), 2L+ UC (approved 04.10.20) 2L/3L HCC 2L NSCLC, 1L HCC, 2L ESCC R/R NK/T-cell lymphoma + chemo 1L Non-Sq. NSCLC (sNDA accepted 06.19.20), 1L Sq. NSCLC (sNDA accepted 04.04.20) 1L NPC, 1L SCLC, Stage II/IIIA NSCLC, Localized ESCC 1L GC, 1L ESCC + pamiparib (PARP) Solid tumors + zanubrutinib (BTK) B-cell malignancies pamiparib (PARP) Monotherapy 1L platinum-sensitive GC maintenance 2L platinum-sensitive OC maintenance 3L gBRCA+ OC HER2- BRCA mutated breast cancer Solid tumors + TMZ (chemo) Solid tumors + RT/TMZ (RT/chemo) Glioblastoma lifirafenib (RAF Dimer) Monotherapy B-Raf- or K-RAS/N-RAS-mutated solid tumors B-Raf- or K-RAS/N-RAS-mutated solid tumors BGB-A333 (PD-L1) monotherapy & + tislelizumab Solid tumors BGB-A425 (TIM-3) monotherapy & + tislelizumab Solid tumors ociperlimab (BGB-A1217, TIGIT) + tislelizumab Solid tumors BGB-A445 (OX40) + tislelizumab Solid tumors BGB-11417 (Bcl-2) monotherapy & + zanubrutinib B-cell malignancies BGB-10188 (PI3-Kδ) mono; + tislelizumab; + zanubrutinib B-cell malignancies; Solid tumors BGB-15025 (HPK1) monotherapy & + tislelizumab IND enabling studies ongoing Global China
17 BeiGene’s Collaborative Pipeline Over 20 compounds * 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 approvals. ^ BiTE, ^^ HLE BiTE, † ZW25, AML: acute myeloid leukemia, HLE BiTE: Half-life extended Bi-specific T-cell engagers, 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 (TARGET) / PROGRAM DOSE ESC. DOSE EXPANSION PIVOTAL COMMERCIAL RIGHTS PARTNER PH1a PH1b PH2* PH2** PH3 Sotorasib (KRAS G12C) Solid Tumors, NSCLC, CRC China Amgen AMG 701^^ (BCMA) MM AMG 176 (Mcl-1, SM (i.v.)) Hematologic malignancies AMG 397 (Mcl-1, SM (oral)) Hematologic malignancies AMG 330^ (CD33) Myeloid malignancies AMG 673^^ (CD33) AML AMG 427^^ (FLT3) AML AMG 596^ (EGFRvIII) Glioblastoma AMG 757^^ (DLL3) SCLC AMG 160^^ (PSMA) Prostate cancer AMG 506 (FAP x 4-1BB, DARPin®) Solid Tumors AMG 199^^ (MUC17) GC/GEJC Sitravatinib (multi-kinase inhibitor) + tislelizumab NSCLC, RCC, OC, MEL Asia ex-Japan, AU, NZ Mirati Mono, + tislelizumab HCC, GC/GEJC Zanidatamab† (HER2, bispecific antibody) Breast cancer, GEA Asia ex-Japan, AU, NZ Zymeworks Biliary tract cancers ZW49 (HER2, bispecific ADC) HER2-expressing cancers Asia ex-Japan, AU, NZ Zymeworks BGB-32451 (B-RAF) Solid tumors Asia ex-Japan SpringWorks1 BA3017 (CTLA4) Mono, + tislelizumab Phase 1 study startup ongoing Global BioAtla SEA-CD70 (anti-CD70) MDS, AML Asia ex-Japan, AU, NZ Seagen DKN-01 (DKK1) + tislelizumab ± chemo 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 Global China
18 Striving to Be the Partner of Choice Leveraging China for global clinical development ADC: antibody-drug conjugate; HER2: human epidermal growth factor receptor 2. • Potential to accelerate global trials through heavily China-inclusive clinical development – Hard-to-recreate ability, and scale – Leader for innovative science-based commercial sales in China – Portfolio of backbone agents with strong synergies for combinations • Amgen collaboration validates clinical and commercial platforms and expands our portfolio • Continue to have capacity available for additional collaborations – First-in-class compounds: KRAS inhibitor sotorasib (Amgen) – Differentiated agents: bi-specific HER2 antibody and ADC (Zymeworks) – Combination opportunities: multi-kinase inhibitor sitravatinib (Mirati) – New market growth: inhibitor for chronic Hepatitis B Infection (Assembly Biosciences) Agreement: January 2018 Agreement: November 2018Agreement: July 2017 Agreement: March 2019 Agreement: April 2019 Agreement: November 2019 Agreement: January 2020Agreement: October 2019 Agreement: January 2020 Agreement: July 2020 Agreement: August 2020
19 Financial Summary Selected Financials Three Months Ended Nine Months Ended Amounts in millions of U.S. dollars Sept 30, 2020 (unaudited) Sept 30, 2019 (unaudited) Sept 30, 2020 (unaudited) Sept 30, 2019 (unaudited) Total Revenue $ 91 $ 50 $ 209 $ 371 Product revenue, net 91 55 209 166 Collaboration revenue -- -- -- 206 Total Expenses (531) (362) (1,382) (943) Cost of sales – products (21) (20) (50) (53) Research and development (349) (237) (939) (644) Selling, general and administrative (161) (105) (392) (245) Net loss attributable to BeiGene, Ltd. $ (425) $ (307) $ (1,124) (561) Cash, cash equivalents, restricted cash and short-term investments $ 4,724 $ 1,277 $ 4,724 $ 1,277 Cash used in operations1 $ (346) $ (265) $ (951) $ (483) 1. Cash used in operations for the quarters ended September 30, 2020 and September 30, 2019 exclude capital expenditures of $28.68 million and $30.87 million, respectively. Cash used in operations for the quarter ended September 30, 2019 includes $36.56 million of accrued interest paid to Guangzhou High-tech Zone Technology Group Co., Ltd. in connection with the repayment of the Shareholder Loan. Cash used in operations for the nine-month periods ended September 30, 2020 and September 30, 2019 exclude capital expenditures of $82.82 million and $74.15 million, respectively, and up-front payments of $43.00 million and $49.00 million, respectively. $2.07 billion cash received from registered direct offering in July 2020
20 Upcoming Milestones and Catalysts BRUKINSA® (zanubrutinib, BTK Inhibitor) Timing Regulatory Regulatory Regulatory Regulatory Data Data Enrollment Continue discussion of ASPEN data with U.S. FDA File sNDA for MZL in China Potential sNDA approval for WM in China; potential approvals in Canada, Australia, Israel CHMP opinion on MAA filing for WM in EU Topline result of Phase 3 SEQUIOIA trial in 1L CLL/SLL Topline result of Phase 3 ALPINE trial in R/R CLL/SLL Complete enrollment of Phase 2 trial in R/R FL 1Q21 1H21 2021 2H21 as early as 2021 1H22 2021 Tislelizumab (PD-1 Antibody) Regulatory Regulatory Data Data Data Data Enrollment sNDA submission for MSI-H in China Potential sNDA approvals in 1L sq and 1L non-sq NSCLC and 2L/3L HCC in China Topline result of Phase 3 trial in 1L HCC Topline result of Phase 3 trial in 2L ESCC Topline result of Phase 3 trial in 1L NPC Present Phase 3 data in 2L NSCLC at an upcoming medical conference Complete enrollment of Phase 3 trials in 1L GC, 1L SCLC and early line ESCC 1H21 2021 2021 or 1H22 1Q21 1H21 1H21 1H21 Pamiparib (PARP inhibitor) Regulatory Data Potential NDA approval for 3L OC in China Topline result of Phase 3 trial in 2L plat-sensitive OC maintenance 1H21 2021 Other Internally Developed Assets Data Data Enrollment Enrollment Present Phase 1 data of BGB-A1217 (TIGIT) mono and in combination with tislelizumab Present Phase 1 data of BGB-11417 (Bcl-2) mono and in combination with zanubrutinib Initiate Phase 3 pivotal program for BGB-A1217 Initiate Phase 1 trial of BGB-15025 (HPK-1) in solid tumors 2021 2H21 1H21 1Q21
21 Upcoming Milestones and Catalysts Partnered Assets Timing Regulatory Regulatory Regulatory Regulatory Data Enrollment Potential approval of QARZIBA for high-risk neuroblastoma in China Potential approval of KYPROLIS for R/R MM in China Potential approval of SYLVANT for multicentric Castleman’s disease in China Potential approval of BAT1706 (Avastin biosimilar) in China Present Phase 1 data of sitravatinib in combination with tislelizumab at an upcoming medical conference Initiate Phase 3 trial of zanidatamab (ZW25) in combination with tislelizumab and chemo in 1L HER2+ GEC 2H21 2021 2H21 2021 1H21 2H21
22 Key Takeaways • BeiGene has an established platform to leverage the highly impactful developments in China – Strategic collaboration with Amgen provides validation of our clinical and commercial capabilities • A compelling emerging growth story with up to 12 products on market by YE 2021 – Robust upcoming news flow from clinical readouts of more than 10 Phase 3 or potentially registration-enabling trials, including indications with large market opportunities (BRUKINSA in CLL and tislelizumab in 1L NSCLC in China) • Diverse early-stage pipeline of assets drives long-term potential upside, including: • On this journey BeiGene is striving to: – Become an oncology and scientific leader – Expand beyond oncology into other areas of need – Continue to build sustainable and competitive advantages – Become the best global clinical organization – addressing the biggest issue in the industry – Transform the industry to bring better medicines to more patients more affordably Sitravatinib (multi-kinase inhibitor) Ociperlimab, (BGB-A1217, TIGIT antibody) Zanidatamab, ZW49 (bispecific HER2 antibody and ADC) BGB-A445 (non-ligand competing OX40 agonist antibody) Sotorasib (KRAS G12C inhibitor) BGB-11417 (Bcl-2 inhibitor)
24 Overview of Zanubrutinib (BGB-3111) Potentially best-in-class BTK inhibitor 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 • Clinical experience to date supports best-in-class hypothesis – ASPEN primary endpoint numerically favorable but not statistically significant – ASPEN: Demonstrated clinically meaningful and favorable differences in safety vs. ibrutinib; Early, landmark PFS and OS analyses are directionally consistent with higher VGPR rate observed in zanubrutinib arm – Strong suggestion of deeper responses in WM and MCL – Favorable response rate, depth, and durability in CLL/SLL – High overall and complete response rates in FL with obinutuzumab combination – Low rate of toxicity/tolerability-related discontinuation DEVELOPMENT PLAN • Fast Track in WM and MZL, and Breakthrough Therapy in MCL designations • Global registrational trials: WM (H2H vs. ibrutinib), 1L CLL/SLL (vs. BR), R/R CLL/SLL (vs. ibrutinib), 1L MCL (R+zanu vs. BR), R/R FL (potential for global first-in-class BTK approval in FL); and R/R MZL (global pivotal Ph 2 trial) • China registration trials for WM MILESTONES AND STATUS • U.S. FDA accelerated approval for use in R/R MCL 11.14.19 • China NMPA approval for use in R/R MCL and R/R CLL/SLL 06.03.20 • Filings accepted: WM: Australia, Canada, China, and EU; MCL: Australia, Israel
25 Zanubrutinib Clinical Program * 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 approvals. 1. as of 06.15.20. 2. global study and potentially registration-enabling in certain countries; DLBCL: Diffuse Large B-cell Lymphoma. *** U.S. only. PROGRAM (TARGET) DOSE ESCALATION DOSE EXPANSION PIVOTAL FILED MARKET*** PH1a PH1b PH2* PH2** PH3 zanubrutinib (BGB-3111, BTK) R/R MCL (Accelerated approval by US FDA 11.14.19, filings accepted in other geographies) R/R MCL (Approved by NMPA 06.03.20) R/R CLL/SLL (Approved by NMPA 06.03.20) R/R WM various geographies TN CLL/SLL: zanubrutinib vs. BR, SEQUOIA R/R CLL/SLL: zanubrutinib vs. ibrutinib, ALPINE TN MCL: zanubrutinib + R vs. BR, MANGROVE R/R MZL2 MAGNOLIA Previously treated CLL/SLL (ibrutinib intolerant) R/R WM R/R DLBCL B-cell malignancies + GAZYVA® (CD20) R/R FL2: zanubrutinib + GAZYVA® vs. GAZYVA® B-cell malignancies + GAZYVA® + venetoclax (CD20 + BCL2) TN CLL/SLL + tislelizumab (PD-1) Hematological tumors + ME-401 (PI3-Kδ) R/R CLL/SLL or B-cell malignancies + BGB-11417 (Bcl-2 inhibitor) B-cell malignancies + lenalidomide +/- ritux. R/R DLBCL Global China
0 100 200 300 400 500 600 700 0 6 12 18 24 Time post-dose (hours) Series1 0 100 200 300 400 500 600 700 0 6 12 18 24 Time post-dose (hours) Series1 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 exposure of zanubrutinib at 40mg QD appears to be comparable to that of ibrutinib at 560mg • Distinct profile compared to acalabrutinib which has a short half-life (1 hour)2 and lower in vitro BTK inhibition IC501-4 • In vitro BTK inhibition IC50 relative to ibrutinib: 1.11 (zanubrutinib) and 3.42–7.23 (acalabrutinib) zanubrutinib ibrutinib acalabrutinib Adapted from Byrd et al., NEJM, 2016 0 100 200 300 400 500 600 700 0 6 12 18 24 P la s m a C o n c e n tr a ti o n ( n g /m L ) Time post-dose (hours) Series1 Series2 Series3 Series4 Ph3 Dose: • 160mg BID Ph3 Dose: • 100mg BID Approved Doses: • 420mg QD for CLL/WM • 560mg QD for MCL/MZL Data from separate Ph1/2 trials^ 26 Zanubrutinib – Pharmacokinetics Profile ^Cross-trial comparison Source: 1. Tam et al., ASH, 2015; 2. Byrd et al., NEJM, 2016; 3. Lannutti et al., AACR, 2015, 4. BeiGene data
27 ASPEN Topline Efficacy Summary Response Rate* Relapsed or Refractory† Overall† Overall August 2019‡ Overall January 2020^ Zanubrutinib (N = 83) Ibrutinib (N = 81) Zanubrutinib (N = 102) Ibrutinib (N = 99) Zanubrutinib (N = 102) Ibrutinib (N = 99) Zanubrutinib (N = 102) Ibrutinib (N = 99) CR 0 0 0 0 0 0 0 0 VGPR 28.9 19.8 28.4 19.2 28.4 17.2 30.4 18.2 PR 49.4 60.5 49.0 58.6 48.0 59.6 48.0 59.6 MR 15.7 13.6 16.7 15.2 18.6 17.2 16.7 16.2 No response 4.8 4.9 4.9 5.0 3.9 5.0 1.0 2.0 VGPR+CR rate, % 28.91 19.81 28.4 19.2 28.4 17.2^^ 30.4 18.2 VGPR+CR rate difference 10.2 p-value2 = 0.0921 12.1 p-value2 = 0.0437 13.2 p-value2 = 0.0302 * Groups were generally well-balanced for number of prior therapies, IPSS score, baseline IgM, and baseline hematologic parameters. Overall CXCR4 mutation was 10.9%. 1. 2-sided p=0.1160. 2. 2-sided descriptive. † Source: IRC Data, data cutoff August 31, 2019. ^ Source: Tam et. al., ASCO 2020, Investigator-Assessed Data, VGPR+CR rate difference adjusted for stratification and age group. p-value for descriptive purpose only. ^^Excluded two patients with VGPR by IRC: MR (EMD present) and PR (IgM assessment by local SPEP M-protein). Primary Endpoint
28 ASPEN: Progression-Free and Overall Survival in ITT population Source: Tam et. al., ASCO 2020 IRC, independent review committee; VGPR, very good partial response. Disease progression determined by IRC. No. of Subjects at Risk No. of Subjects at Risk Event-free rates at 12 months 89.7% versus 87.2% Event-free rates at 12 months 97.0% versus 93.9%
29 ASPEN Topline Safety: Overall Summary Category, n (%) Overall Ibrutinib (n = 98) Zanubrutinib (n = 101) Patients with ≥ 1 AE 97 (99.0) 98 (97.0) Grade ≥3 62 (63.3) 59 (58.4) Serious 40 (40.8) 40 (39.6) AE leading to death 4 (4.1) a 1 (1.0) b AE leading to treatment discontinuation 9 (9.2) c 4 (4.0) d AE leading to dose reduction 23 (23.5) 14 (13.9) AE leading to dose held 55 (56.1) 47 (46.5) Patients with ≥ 1 treatment-related AE 84 (85.7) 80 (79.2) Patients with ≥ 1 AE of interest 81 (82.7) 86 (85.1) Source: Tam et. al., ASCO 2020. AE, adverse event (treatment-emergent); G, grade. a cardiac failure acute; sepsis (n=2); unexplained death. b cardiac arrest after plasmapheresis cG5 sepsis (n=2); G5 unexplained death; G3 acute myocardial infarction; G3 hepatitis ; G3 pneumonia; G2 drug-induced liver injury; G2 pneumonitis; G1 pneumonitis. dG5 cardiac arrest after plasmapheresis; G4 neutropenia; G4 subdural hemorrhage ; G2 plasma cell myeloma.
Source: Tam et. al., ASCO 2020. Higher AE rate in bold red with ≥10% difference in any grade or ≥5% difference in grade 3 or above. No tumor lysis syndrome was reported. Opportunistic infection ibrutinib (n=2), zanubrutinib (n=1). AE, adverse event; BTKi, Bruton tyrosine kinase inhibitor; PT, preferred term. *Defined as any grade ≥3 hemorrhage or any grade central nervous system hemorrhage. †Descriptive 2-sided P<0.05. ‡Including PT terms of neutropenia, neutrophil count decreased, febrile neutropenia, agranulocytosis, neutropenic infection, and neutropenic sepsis. 30 ASPEN Adverse Events of Special Interest All Grades Grade ≥3 AE Categories, n (%) (Pooled Terms) Ibrutinib (n=98) Zanubrutinib (n=101) Ibrutinib (n=98) Zanubrutinib (n=101) Atrial fibrillation/flutter† 15 (15.3) 2 (2.0) 4 (4.1) 0 (0.0) Diarrhea (PT) 31 (31.6) 21 (20.8) 1 (1.0) 3 (3.0) Hemorrhage 58 (59.2) 49 (48.5) 8 (8.2) 6 (5.9) Major hemorrhage* 9 (9.2) 6 (5.9) 8 (8.2) 6 (5.9) Hypertension 17 (17.3) 11 (10.9) 12 (12.2) 6 (5.9) Neutropenia†,‡ 13 (13.3) 30 (29.7) 8 (8.2) 20 (19.8) Infection 66 (67.3) 67 (66.3) 19 (19.4) 18 (17.8) Second malignancy 11 (11.2) 12 (11.9) 1 (1.0) 2 (2.0)
31 ASPEN: Time to AE – Risk Analysis Over Duration of Treatment Source: Tam et. al., ASCO 2020. AE, adverse event. *Descriptive purpose only. Kaplan-Meier Curve: Time to Atrial Fibrillation / Flutter P value <0.05* Kaplan-Meier Curve: Time to Hypertension P value = 0.16*
32 Data Suggest Activity in Difficult to Treat WM MYD88WT Patients Sources: 1 Tam et. al. ASCO 2020, Data cut: Aug 31, 2019, Safety summary above; 2 Tam et al, EHA 2019. * Follow up for full WM cohort. ASPEN cohort 2 safety summary. The most frequently reported adverse events (AEs) were diarrhea, anemia, contusion, pyrexia, and upper respiratory tract infection. Major hemorrhage was reported in 2 patients, and atrial fibrillation was reported in 1 patient. There were no fatal AEs. Phase 1 safety summary for full WM n=77 cohort. Patients with an event n (%): Patients with ≥1 AE grade ≥3 40 (51.9); Patients with ≥1 serious AE 363 (46.8); AE leading to treatment discontinuation 82 (10.4); Fatal AE 5c (6.5). 3Includes serious AEs possibly related to zanubrutinib (n=6): hemothorax+pleural effusion+anemia (n=1), atrial fibrillation (n=1), colitis (n=1), febrile neutropenia (n=1), pneumonia (n=1), and cellulitis (n=1); septic arthritis relatedness was unknown. 2Abdominal sepsis (fatal), septic arthritis (fatal), worsening bronchiectasis (fatal), gastric adenocarcinoma (fatal), prostate adenocarcinoma, metastatic neuroendocrine carcinoma, acute myeloid leukemia, and breast cancer (each n=1). Best response, n (%) ASPEN cohort 21 (n=26) Phase 12 (n=8) ASCO 2020 EHA 2019 ORR 21 (80.8) 7(87.5) MRR 14 (53.9) 5(62.5) CR / VGPR 7 (26.9) 2(25.0) PR 6 (23.1) 3(37.5) MR 8 (30.8) 2(25.0) SD 4 (15.4) 1(12.5) PD 1 (3.8) 0 Median Follow-up months (range) 17.9 (2.3 - 21.7) 24.3 (4.1-45.7)*
33 Zanubrutinib Efficacy in R/R MCL From U.S. approved label The most common adverse reactions (> 10%) with BRUKINSA were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, blood in the urine (hematuria), fatigue, constipation, and hemorrhage. The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%). Of the 118 patients with MCL treated with BRUKINSA, eight (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B). Source: BRUKINSATM U.S. label; * FDG-PET scans were not required for response assessment; RR: relapsed refractory; NE: not estimable; DoR: duration of response. Best Response Zanubrutinib RR RR Source Study BGB-3111-206 Ph2 study BGB-3111-AU-003 Ph1/2 study Evaluable for efficacy, n 86 32 Median DoR in months 19.5 (16.6, NE) 18.5 (12.6, NE) Response Criteria Lugano 2014 Median Prior Lines of Therapy 2 (1-4) 1 (1-4) ORR 84% 84% CR 59% 22%* PR 24% 62%
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%) 34 Zanubrutinib Efficacy in CLL/SLL Frequent and durable responses – Phase 1/2 Source: Seymour et al. 14-ICML 2017 (abstract 237) poster; *Discontinuation prior to first assessment Progression Free Survival (PFS)Overall Response Rate (ORR) P ro b a b il it y o f P ro g re s s io n -f re e S u rv iv a l (% ) No. of Subjects at Risk Month 66 66 62 53 45 37 27 25 19 11 9 6 4
zanubrutinib Total CLL n 91 Median follow-up (mo) 15.1 Best Response ORR CR PR PR-L SD Non-evaluablea 77 (84.6%) 3 (3.3%) 54 (59.3%) 20 (22.0%) 4 (4.4%) 3 (3.3%) 35 Zanubrutinib Efficacy in CLL/SLL Frequent and durable responses – Phase 2 Source: Xu et al. 15-ICML 2019; aMissing anatomy imaging for 2 patients, and without evidence of response maintenance for at least 2 months for 1 patient, separately. Progression Free Survival by IRC (PFS)Best Overall Response by IRC (ORR)
36 Ibrutinib Efficacy in CLL/SLL Source: For TN, Burger, et al New Engl J Med 2015. For R/R, Byrd, et al New Engl J Med 2013 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-L SD PD 75 (88%) 2 (2%) 58 (68%) 15 (18%) NR NR Overall Response Rate (Treatment-Naïve) P ro b a b il it y o f P ro g re s s io n -f re e S u rv iv a l P ro b a b il it y o f P ro g re s s io n -f re e S u rv iv a l (% )
Treatment-Naïve (n=80) Relapsed/Refractory (n=536) Total (n=616) Median Follow-Up 14.5 months Total Treatment Discontinuation 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 Unrelated to Treatment 1 (1%) 28 (5%) 29 (5%) Physician or Patient Decision 2 (2%) 15 (3%) 17 (3%) Transplant 0 (0%) 8 (1.5%) 8 (1%) Financial Concerns 0 (0%) 1 (0.2%) 1 (0.2%) Secondary Malignancy 1 (1%) 2 (0.5%) 3 (0.5%) 37 Ibrutinib Discontinuation for toxicity or progression in CLL/SLL Source: Mato ASH 2016; Note: at med follow-up 24.5 mos, 22% discontinuation rate with acalabrutinib in R/R CLL; 9% AE-related, 8% PD-related. Byrd ASH 2017.
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%) 38 Zanubrutinib Discontinuation for toxicity or progression in CLL/SLL is uncommon Source: Seymour, ICML 2017
• Very low rates of headache and hypertension (6.7% and 6.3%) • Concomitant use of anti-coagulants was allowed in these zanubrutinib trials • Low rate of treatment discontinuation for drug-related adverse events Adverse Events of Interest for BTK Inhibitors in Patients Treated with Zanubrutinib AE of Interest (All Causes)1 Zanubrutinib (Including Patients Enrolled in Combo Studies) Patient Number N=641 Mean Exposure Time 7.7 mo Atrial Fibrillation 1.7% Major Hemorrhage 1.9% AE of Interest (All Causes)2 Zanubrutinib (Single Agent Only) Patient Number N=682 Median Exposure Time 13.4 mo Atrial Fibrillation (Gr ≥3) 1.9% (0.6%) Major Hemorrhage* 2.5% (2.1%) Diarrhea (Gr ≥3) 19.4% (0.9%) 39 Zanubrutinib Safety and tolerability summary; over 600-patient experience Major hemorrhage includes serious or grade ≥3 bleeding of any site, or central nervous system bleeding of any grade. Source: pooled safety analysis of ongoing zanubrutinib clinical trials; 1 Seymour, ICML 2017; 2 Tam et, al., EHA 2019 (Data cut-off dates: BGB-3111-207: Sept 2018; BGB-3111 AU-003, -1002, -205 and 210: Dec 2018; BGB-3111-206: Feb 2019)
40 Zanubrutinib Responses Across Additional B-Cell Malignancies Sources: 1. Tam et. al., ASH 2017; 2. Song et al., ICML 2019; 3. Tam et al., ICML 2019; 4. Song et. al., CSCO 2018; 5. Tedeschi et al, EHA 2020; * CT response assessment; ** PET-CT response assessment. MZL MCL MCL FL FL DLBCL Source EHA 20205 ICML 20193 China pivotal data ASH20182 ASH 20171 CSCO 20184 ASH 20171 n 20 48 85 17 26 26 Follow-up (med) 27.1 mo 16.7 mo 35.9 wk 7.8 mo 9.5 mo 4.2 mo Prior Lines (med) 2 (1-5) 1 (1-4) 2 (1-4) 2 (1-8) 3 (1-9) 2 (1-10) ORR 80% 85% 84% 41% 42% 31% CR 15% 29%* 59%** 18% 8% 15% VGPR -- -- -- -- -- -- PR/PR-L 65% 56% 25% 24% 35% 15% MR -- -- -- -- -- -- • Despite relatively early follow-up, responses were observed in multiple B-cell malignancies • Consistency across tumor types suggests that zanubrutinib is a highly active BTK inhibitor
• Overall response rate and complete responses to date compare favorably to those achieved with respective single-agents and recently approved therapies FL Zanubrutinib + Obinutuzumab Zanubrutinib Ibrutinib Obinutuzumab Idelalisib Source ICML 20191 ASH 20172 ASH 20163 JCO 20134 NEJM 20145 n 36 17 110 34 72 Population prior alkylator and CD20, mixed rituximab-sensitive and -refractory median 2 prior lines of therapy, range 1-8 prior alkylator and CD20, last response <12 months mixed rituximab- sensitive and - refractory alkylator and rituximab-refractory relapse Follow-up (med) 20.1 mo 7.8 mo 27.7 mo 33.7 mo NR ORR 72% 41% 21% 50% 54% CR 39% 18% 11% 18%6 6% Data from separate trials 41 Zanubrutinib Plus Obinutuzumab Combination in Follicular Lymphoma Sources: 1. Tam et al., ICML 2019; 2. Tam et al., ASH (abstract 152), 2017; 3. Gopal, et al ASH 2016; 4. Salles, et al J Clin Oncol 2013; 5. Gopal, et al N Engl J Med 2014; 6. 18% represents complete response rate in the 40 indolent lymphoma patient population that include 34 FL patients. Note: data on slide are cross-trial comparison;
Treatment Cycle: C1 C2 C3 C4 C5 C6 C7 C8 C9+ Venetoclax: Ramp-Up to Target 400 mg QD Zanubrutinib: 160mg BID Obinutuzumab 1000mg on /cycle 1 D1b/8/15, and Cycles 2–8 D1 PB MRD: X X X X X BM MRD: X X XC XC CT imaging: X X XC XC 42 BOVen: Treatment Schema a. Once peripheral blood (PB) uMRD is determined and confirmed in bone marrow (BM), patients complete 2 additional cycles followed by confirmatory MRD peripheral blood testing; if PB uMRD x 2 and BM uMRD x 1, therapy is discontinued. b. Obinutuzumab split over days 1-2 of cycle 1 if ALC >25,000. c. BM biopsy obtained at Screening and C3D1; thereafter BM is only obtained if PB-uMRD. CT imaging obtained at Screening, C3D1, C7D1, EOT, then every 6 months during post-treatment surveillance. BOVen discontinued if: • Prespecified uMRD end pointa • Min 8 cycles; Max 24 cycles (if needed)
43 BOVen: Achieved Rapid Undetectable MRD • Follow up: 11 months (2-14+) • Median time to uMRD in marrow: 6 months (2-14+) • 62% (23/37) met the uMRD endpoint and have stopped therapy at median 8 months (6 months of triplet) 2 months 4 months 6 months 8 months PR uMRD BM uMRD 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2.7% (1/37) 27.8% (10/36) 55.6% (20/36) 77.1% (27/35) 83.8% (31/37) 73% (27/37) Total
44 BOVen: Adverse Events of Special Interest BOVen Treatment emergent hematologic and non-hematologic adverse events occurring in ≥5% of patients - Heme: Neutropenia 51.3% (Gr 3+: 15.4%), Thrombocytopenia 46.2% (15.4%), Anemia 18%; Non-Heme: Infusion related reaction 41% (2.6%), Bruising 41%, Diarrhea 41%, Nausea 23.1%, Fatigue 20.5%, Myalgia 15.4%, Rash 12.8% (2.6%), Sinusitis 12.8%, GERD 10.3%, Lung infection 7.7% (5.1%), Abdominal pain 7.7%, Arthralgia 7.7%, Constipation 7.7%, Edema limbs 7.7%, Petechiae 7.7% • Bleeding included one grade 5 ICH on cycle 1 day after initiating intravenous heparin for pulmonary emboli, one grade 1 conjunctival hemorrhage, and one grade 1 vaginal bleeding • Atrial fibrillation occurred in one patient who had a history of prior paroxysmal atrial fibrillation Neutropenia Thrombocytopenia Infusion related reaction Bruising Bleeding Hypertension Atrial fibrillation Febrile neutropenia Tumor lysis syndrome Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 51.3% (Gr 3+: 15.4%) 46.2% (Gr 3+: 5.1%) 41% (Gr 3+: 2.6%) 41% 12.8% (Gr 3+: 2.6%) 5.1% 2.6% 2.6% 0%
45 Ongoing Global Phase 3 Studies ASPEN topline results announced in December 2019 WM=Waldenström’s macroglobulinemia, BID=twice daily, CR=complete response, MUT=mutation, PD=progressive disease, QD=once daily, R=randomization, R/R=relapsed/refractory, TN=treatment naïve, VGPR=very good partial response, WT=wild type. This study is registered at ClinicalTrials.gov (NCT03053440) Cohort 2: WM with wild type MYD88 Cohort 1: R/R or TN* WM with MYD88L265P mutation R 1:1 MYD88MUT WM patients (N=201, 164 R/R) Arm B Ibrutinib 420mg QD until PD Arm A Zanubrutinib 160 mg BID until PD MYD88WT WM patients (N = 26) Arm C Zanubrutinib 160 mg BID until PD *TN must be unsuitable for standard chemoimmunotherapy Zanubrutinib vs. Ibrutinib in WM Primary endpoint: CR or VGPR in R/R and all enrolled patients
46 Ongoing Global Phase 3 Studies in CLL/SLL SEQUOIA and ALPINE 1L=first-line treatment, BID=twice daily, CLL=chronic lymphocytic leukemia, del=deleted, FCR=fludarabine, cyclophosphamide, and rituximab, ORR=overall response rate, PD=progressive disease, PFS=progression- free survival, QD=once daily, R=randomized, SLL=small lymphocytic lymphoma, TN=treatment naïve. These studies are registered at ClinicalTrials.gov (NCT03734016) and (NCT03336333). Primary endpoint: PFS Arm A Zanubrutinib 160 mg BID until PD Previously untreated CLL patients (N=450) Arm B Bendamustine + Rituximab (BR) × 6 cycles Previously untreated 17p del CLL patients (N=110) Arm C Zanubrutinib 160 mg BID until PD R 1:1 Cohort 1: Non–17p del TN CLL Must be not suitable for FCR Zanubrutinib vs. BR in 1L CLL/SLL Zanubrutinib vs. Ibrutinib in R/R CLL/SLL R 1:1 R/R CLL/SLL ≥ 1 prior treatment (N=600) Arm B Ibrutinib 420mg QD (n = 300) Arm A Zanubrutinib 160mg BID (n = 300) Relapsed/Refractory CLL/SLL (received ≥ 1 prior treatments) Primary Endpoint: ORR (non-inferiority and superiority) Cohort 2: 17p del TN CLL Full trial enrollment completed in June 2019 Complete enrollment expected in 2020
47 Ongoing Pivotal Study CLL/SLL=chronic lymphocytic leukemia/small lymphocytic lymphoma, FL=follicular lymphoma, ORR=overall response rate, PD=progressive disease, PFS=progression-free survival, QD=once daily, R=randomization. *Must have received prior treatment with rituximab and an alkylator; relapsed <12 months from end of last treatment OR refractory to last treatment. This study is registered at ClinicalTrials.gov (NCT03332017). R 2:1 Grade 1, 2, or 3a FL patients (N=210) Arm B Obinutuzumab X 6 cycles then q 8 wks until PD (n = 70) Arm A Zanubrutinib 160 QD + Obinutuzumab X 6 cycles then q 8 wks until PD (n = 140) Relapsed/Refractory FL (received ≥2 prior treatments*) Primary Endpoint: ORR Phase 2 Zanubrutinib + Obinutuzumab vs Obinutuzumab in R/R FL
48 Zanubrutinib Potentially Addresses Areas of Need for Patients Treated with BTK Inhibitors Efficacy • Complete and sustained target inhibition may result in better response quality – We are testing this hypothesis in Phase 3 head-to-head trials against ibrutinib in WM and CLL Tolerability • In “real-world” ibrutinib use in CLL, not only acute/ serious toxicities (atrial fibrillation, serious bleeding), but cumulative tolerability issues (myalgia, arthralgia, hypertension) are frequently treatment-limiting • Zanubrutinib to date has been associated with low rates of toxicity-related discontinuations and cumulative “off-target” toxicities1 Drug-Drug Interactions • Based on drug interaction studies, co-administration with strong CYP3A inhibitors is permitted – Includes important agents in management of leukemia/ lymphoma patients, such as azole anti-fungals • Co-administration of proton pump inhibitor (PPIs) or other Acid-Reducing Agents (ARA) does not affect zanubrutinib exposure based on PK models • Patients have been allowed to receive anticoagulants and aspirin on zanubrutinib single arm trials Source: 1. Tam et. al. EHA 2019
49 U.S. BRUKINSA Launch Progress BRUKINSA made commercially available within four days of November 2019 approval 1. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. PPIs = proton pump inhibitors; H2-RAs = H2 receptor antagonists. Josh Neiman Head, U.S. Commercial Flatiron Onyx Pharmaceuticals Genentech BRUKINSA™ (zanubrutinib) received accelerated approval in the U.S. for R/R MCL1 BRUKINSA is the only FDA-approved BTK inhibitor shown to deliver 100% median occupancy in peripheral blood cells and the only BTK inhibitor with the flexibility to be taken once or twice daily • patient support program launched within minutes of approval • Commercial team in field and focused on driving awareness of BeiGene and BRUKINSA • Feedback from clinicians: – Impressed by response rates from 206 and 003 studies – Appreciate QD / BID dosing flexibility and ability to combine with PPIs and H2-RAs – Encouraged by 100% median BTK occupancy – See BRUKINSA as a differentiated BTKi
tislelizumab OVERVIEW • Tislelizumab is a PD-1 checkpoint inhibitor designed to minimize binding to FcγR, which is believed to play an essential role in activating phagocytosis in macrophages to minimize its negative impact on T effector cells.1 – China label data: 77% ORR (62% CR) in R/R cHL • Broad development in Asia-prevalent cancers – 17 ongoing or filed Ph. 3 or potentially registration-enabling trials: 5 in lung cancer, 2 in liver cancer, 3 in esophageal cancer, 1 in gastric cancer, 2 in bladder cancer, 1 in MSI-H or dMMR tumors, 2 in classical Hodgkin’s lymphoma and 1 in nasopharyngeal cancer – Aimed to support broad label and label-based reimbursement • Strong manufacturing capabilities with emphasis on quality – Manufacturing process and initial capacity developed by Boehringer Ingelheim – State-of-the-art facility in Guangzhou CLINICAL DATA • Clinical experience has demonstrated encouraging clinical activity and generally well-tolerated safety profile DEVELOPMENT PLAN • Broad development program designed to capture worldwide commercial opportunities – Two China accelerated approval trials : cHL and urothelial cancer (both approved) – Global Ph2 trials in NK/T cell lymphomas and 2L/3L HCC, China pivotal Ph2 in MSI-H or dMMR solid tumors, 6 global Ph3 trials in 1L GC, 1L and 2L ESCC, 1L HCC and 2L NSCLC; 7 Ph3 trials in 1L non-sq and sq NSCLC, 1L SCLC extensive stage, neoadjuvant stage II/IIIA NSCLC, 1L UC, localized ESCC and 1L NPC in China – Combinations ongoing with BeiGene’s PARP, BTK, PD-L1, TIM3 and TIGIT inhibitors – Additional Ph3 trials planned MILESTONES AND STATUS • NDA in China for R/R cHL approved (priority review) by NMPA 12.27.19; sNDA for 2L+ UC approved (priority review) 04.10.20; sNDA for 1L Squamous NSCLC accepted 04.20.20; sNDA for 1L Non-squamous NSCLC accepted 06.19.20; sNDA for previously treated HCC accepted 07.01.20 50 Overview of Tislelizumab (BGB-A317) Broad integrated global and China development program
51 Tislelizumab Clinical Program Broad development for Asia-prevalent cancers PROGRAM (TARGET) TUMOR DOSE ESCALATION DOSE EXPANSION PIVOTAL FILED MARKET PH1a PH1b PH2* PH2** PH3 tislelizumab (PD-1) Heme R/R cHL (Approved by NMPA 12.27.19) R/R NK/T-cell lymphoma Bladder 2L+ UC (Approved by NMPA 04.10.20) 1L UC Lung 2L NSCLC 1L non-squamous NSCLC (sNDA accepted by NMPA 06.19.20) 1L squamous NSCLC (sNDA accepted by NMPA 04.20.20) 1L SCLC Stage II/IIIA SCLC Liver 1L HCC 2L/3L HCC (sNDA by NMPA accepted 07.01.20)2 Esophageal 2L ESCC 1L ESCC Localized ESCC Gastric 1L GC 1L NPC MSI-H or dMMR solid tumors Solid tumors + pamiparib (PARP) Solid tumors + zanubrutinib (BTK) Hematologic tumors + sitravatinib (multi-kinase) NSCLC, RCC, OC, melanoma^ + sitravatinib (multi-kinase) HCC, GC^ + A333 (PD-L1) Solid tumors + A425 (TIM3) Solid tumors + ociperlimab (TIGIT) Solid tumors +A445 (OX40) Solid tumors Broad development global program with additional Ph3/potential registration-enabling trials planned in lung, gastric, liver, and esophageal cancers *Some indications will not require a non-pivotal Ph2 clinical trial prior to beginning pivotal Ph2 or 3 clinical trials. **Confirmatory clinical trials post-approval are required for accelerated approvals. ^Trials conducted in the APAC region. 1. as of June 14, 2020. 2. global study and potentially registration-enabling in certain countries Global China
52 Tislelizumab’s Lack of FcγR Binding Was Designed to Prevent Macrophage-Mediated T-Cell Clearance We believe the different FcγR design may have meaningful differences in the clinic Sources: Dahan et al., Cancer Cell, 2015; Arlauckas et al., Sci. Transl. Med., 2017; FcγRI=Fc gamma receptor-1, MDSC=myeloid-derived suppressor cell. Fc RI- + Nivolumab Pembrolizum ab CD8+ T cell CD4+ T cell - FcRI Macrophage Monocyte MDSC Dendritic cell + Tislelizuma b Antibody-Dependent Cellular Phagocytosis Based on FcγR Binding Tislelizumab has Minimal FcγRI Binding Thus Abrogating ADCP Activity T cell Macrophage Nivo surrogate 0 200 400 600 800 1000 1200 1400 1600 6 11 16 21 26 M e a n T u m o r V o lu m e ( m m 3 ± S E M ) Treatment Days Vehicle BGB-A317 10mg/kg Nivolumab 10mg/kg Pembrolizumab 10mg/kg * P < 0 .0 5 Dosed Weekly Tislelizumab 10mg/kg Tislelizumab Differential Preclinical Efficacy in in vivo Mouse Tumor Model • Tislelizumab was specifically engineered to minimize binding to FcγR on macrophages, thereby abrogating antibody-dependent cellular phagocytosis (ADCP), a potential mechanism of T-cell clearance • Hypothesis supported by literature: Dahan et al. reported that FcγR engagement compromises the anti-tumor activity of anti-PD-1 Abs; Arlauckas et al. showed in a mouse model that anti-PD-1 Abs could be transferred from PD-1+ T cells to macrophages in FcγR-dependent manner
53 Tislelizumab in 1L Squamous NSCLC: PFS by IRC Source: Wang et. al., ESMO 2020; Abbreviations: CI, confidence interval;PFS, progression-free survival. Arm A: Tislelizumab + paclitaxel carboplatin Arm B: Tislelizumab + nabpaclitaxel carboplatin Arm C: paclitaxel carboplatin
54 Tislelizumab in 1L Squamous NSCLC: Response Source: Wang et. al., ASCO 2020; DCR=CR+PR+SD. *Includes patients with BOR in CR or PR or ≥24 weeks SD. Abbreviations: BOR, best overall response; CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DCR, disease control rate; IRC, Independent Review Committee; ITT, intent-to-treat; nab, nanoparticle albumin-bound; NE, not evaluable; ORR, objective response rate; PC, paclitaxel and carboplatin; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. Arm A Tislelizumab + PC (n=120) Arm B Tislelizumab + nab-PC (n=119) Arm C PC (n=121) BOR, n (%) CR 5 (4) 3 (3) 1 (< 1) PR 82 (68) 86 (72) 59 (49) SD 18 (15) 19 (16) 36 (30) Non-CR/non-PD 0 0 1 (< 1) PD 12 (10) 5 (4) 11 (9) NE/missing 3(3) 6 (5) 13 (11) ORR, % (95% CI) 73 (63.6, 80.3) 75 (66.0, 82.3) 50 (40.4, 58.8) DCR, % (95% CI) 88 (80.2, 92.8) 91 (84.1, 95.3) 80 (71.9, 86.9) CBR, %* (95% CI) 81 (72.6, 87.4) 80 (71.5, 86.6) 56 (46.9, 65.2) Median DoR, months (95% CI) 8.2 (5.0, NE) 8.6 (6.3, NE) 4.2 (2.8, 4.9)
55 Tislelizumab in 1L Squamous NSCLC: Safety Preferred Term, n (%) Arm A Tislelizumab + PC (n=120) Arm B Tislelizumab + nab-PC (n=119) Arm C PC (n=121) All Grades Grades ≥3 All Grades Grades ≥3 All Grades Grades ≥3 Anemia 99 (82.5) 6 (5.0) 104 (88.1) 24 (20.3) 87 (74.4) 11 (9.4) Alopecia 77 (64.2) 0 81 (68.6) 0 72 (61.5) 0 Neutrophil count decreased 75 (62.5) 62 (51.7) 72 (61.0) 54 (45.8) 68 (58.1) 53 (45.3) White blood cell count decreased 63 (52.5) 26 (21.7) 68 (57.6) 32 (27.1) 62 (53.0) 28 (23.9) Leukopenia 57 (47.5) 19 (15.8) 66 (55.9) 30 (25.4) 56 (47.9) 21 (17.9) Neutropenia 51 (42.5) 40 (33.3) 50 (42.4) 32 (27.1) 55 (47.0) 47 (40.2) Decreased appetite 50 (41.7) 1 (0.8) 49 (41.5) 1 (0.8) 35 (29.9) 1 (0.9) ALT increased 48 (40.0) 2 (1.7) 40 (33.9) 2 (1.7) 27 (23.1) 0 Platelet count decreased 40 (33.3) 5 (4.2) 52 (44.1) 16 (13.6) 28 (23.9) 2 (1.7) AST increased 39 (32.5) 0 38 (32.2) 1 (0.8) 13 (11.1) 0 Nausea 34 (28.3) 0 48 (40.7) 0 29 (24.8) 1 (0.9) Thrombocytopenia 33 (27.5) 7 (5.8) 47 (39.8) 15 (12.7) 32 (27.4) 7 (6.0) Pain in extremity 33 (27.5) 3 (2.5) 8 (6.8) 0 23 (19.7) 0 Blood bilirubin increased 27 (22.5) 0 14 (11.9) 0 15 (12.8) 0 Asthenia 26 (21.7) 0 19 (16.1) 0 23 (19.7) 1 (0.9) Hypoesthesia 25 (20.8) 0 11 (9.3) 0 19 (16.2) 0 Vomiting 24 (20.0) 0 22 (18.6) 0 15 (12.8) 2 (1.7) Source: Wang et. al., ASCO 2020; Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; nab, nanoparticle albumin-bound; PC, paclitaxel and carboplatin; TEAE, treatment-emergent adverse event, TRAE, treatment-related adverse event. TRAEs Associated With Any Study Component and Occurring in ≥ 20% in Any ArmOverall Summary Arm A Tislelizumab + PC (n=120) Arm B Tislelizumab + nab-PC (n=119) Arm C PC (n=121) Patients with ≥ 1 TEAE 120 (100.0) 117 (99.2) 117 (100.0) Serious TEAE 44 (36.7) 45 (38.1) 29 (24.8) TEAE leading to permanent discontinuation of any study treatment component 15 (12.5) 35 (29.7) 18 (15.4) TEAE leading to death 4 (3.3) 5 (4.2) 5 (4.3) • Investigator-assessed TEAEs related to any study treatment were reported in 99.2%, 99.2%, and 100% of patients in Arms A, B, and C, respectively • The most commonly reported treatment-related AEs (TRAEs) associated with any study component were mainly hematologic in nature Data presented as n (%).
56 Tislelizumab in 1L Non-Squamous NSCLC: PFS by IRC Source: Lu et. al., ESMO 2020; Abbreviations: CI, confidence interval; IRC, Independent Review Committee; PFS, progression-free survival.
57 Tislelizumab in 1L Non-Squamous NSCLC: Best Overall Response Source: Lu et. al., ESMO 2020; CI, confidence interval; CR, complete response; IRC, Independent Review Committee; NE, not estimable; ORR, objective response rate; PR, partial response.
58 Tislelizumab in 1L Non-Squamous NSCLC: Safety Preferred Term, n (%) Arm A Tislelizumab + PP (n=222) Arm B PP (n=110) Grade 1-2 Grade ≥3 Grade 1-2 Grade ≥3 Anemia1 151 (68.0) 30 (13.5) 71 (64.5) 11 (10.0) Leukopenia2 135 (60.8) 48 (21.6) 65 (59.1) 16 (14.5) Thrombocytopenia3 112 (50.5) 43 (19.4) 55 (50.0) 15 (13.6) Nausea 94 (42.3) 1 (0.5) 43 (39.1) 1 (0.9) Alanine aminotransferase increased 92 (41.1) 8 (3.6) 45 (40.9) 3 (2.7) Aspartate aminotransferase increased 86 (38.7) 4 (1.8) 49 (44.5) 0 Neutropenia4 83 (37.4) 99 (44.6) 42 (38.2) 39 (35.5) Fatigue5 74 (33.3) 3 (1.4) 35 (31.8) 1 (0.9) Decreased appetite 63 (28.4) 3 (1.4) 28 (25.5) 1 (0.9) Vomiting 55 (24.8) 1 (0.5) 23 (20.9) 1 (0.9) Source: Lu et. al., ESMO 2020; Data presented as n (%). 1, Anemia included reports of anemia, hemoglobin decreased, and red blood cell count decreased. 2, Leukopenia included reports of white blood cell count decreased and leukopenia. 3, Thrombocytopenia included reports of platelet count decreased and thrombocytopenia. 4, Neutropenia included reports of neutrophil count decreased and neutropenia. 5, Fatigue included asthenia, fatigue, and malaise. Abbreviations: PP, pemetrexed+platinum. Incidence of Treatment-Related Adverse Events Occurring in ≥20% of Patients Treated With Tislelizumab Plus Chemotherapy or Chemotherapy Alone Treatment of tislelizumab in combination with platinum and pemetrexed was generally well-tolerated, with no new safety signals identified; All patients in Arm A and 99.1% of patients in Arm B experienced at least one treatment-emergent adverse event (TEAE); TEAEs leading to permanent discontinuation of any component of treatment occurred in 25.7% and 9.1% of the patients in Arm A and Arm B, respectively; Most treatment-related adverse events (TRAEs) were hematologic in nature and primarily mild-to-moderate in severity, as follows: In Arm A, the most common (≥20.0%) Grade 1-2 TRAEs include anemia (68.0%), leukopenia (60.8%), thrombocytopenia (50.5%), nausea (42.3%), increased alanine aminotransferase (ALT; 41.4%), increased aspartate aminotransferase (AST; 38.7%), neutropenia (37.4%), fatigue (33.3%), decreased appetite (28.4%), and vomiting (24.8%); In Arm B, the most common (≥20.0%) Grade 1-2 TRAEs include anemia (64.5%), leukopenia (59.1%), thrombocytopenia (50.0%), increased AST (44.5%), increased ALT (40.9%), nausea (39.1%), neutropenia (38.2%), fatigue (31.8%), decreased appetite (25.5%), and vomiting (20.9%); Grade ≥3 TRAEs occurred in 67.6% of patients in Arm A and 53.6% in Arm B, with the most common (≥10.0%) in Arm A being neutropenia (44.6%), leukopenia (21.6%), thrombocytopenia (19.4%), and anemia (13.5%), and the most common (≥10.0%) in Arm B being neutropenia (35.5%), leukopenia (14.5%), thrombocytopenia (13.6%), and anemia (10.0%); Immune-mediated AEs were reported in 57 patients in Arm A (25.7%), and most of them were mild-to-moderate in severity, with the most common ones being pneumonitis (9%), hypothyroidism (8.6%), and hyperthyroidism (2.7%); and Across the trial, nine patients experienced a fatal TEAE, including seven in Arm A caused by pneumonitis (n=3), asphyxia, atrial fibrillation, cerebellar hemorrhage, and unspecified death (n=1, each), and two in Arm B caused by pneumonitis and embolism (n=1, each).
IRC Dataset cHL Enrolled Patients N=70 Median Follow-up 13.9 months Prior Lines, Median (range) 3 (2-11) ORR 87.1% CR 62.9% PR 24.3% -- Majority of transplant-ineligible patients had failed to respond to salvage chemotherapy Baseline Characteristics Total (N=70) Age (years), median (range) 32.5 (18, 69) Age group <65 / 65-74 years, n (%) 66 (94.3) / 4 (5.7) Sex, male / female, n (%) 40 (57.1) / 30 (42.9) Time since first diagnosis of cHL (months), median (range) 25.33 (4.6, 262.3) Stage IV at study entry, n (%) 42 (60.0) Bulky disease*, n (%) 8 (11.4) Bone marrow involvement, n (%) 22 (31.4) B-symptom(s), n (%) 26 (37.1) Ineligible for prior ASCT†, n (%) Failure to achieve an objective response to salvage chemotherapy 53 (75.7) Inadequate stem cell collection or unable to collect stem cells 2 (2.9) Co-morbidities 2 (2.9) Prior lines of systemic therapy, median (range) 3 (2-11) Type of prior therapy, n (%) Chemotherapy 70 (100.0) Radiotherapy 21 (30.0) ASCT 13 (18.6) Immunotherapy‡ 15 (21.4) Brentuximab vedotin 4 (5.7) 59 Tislelizumab China cHL Pivotal Trial Data Deep and frequent responses observed in both transplant-ineligible patients and patients who failed transplant Source: Song et al., EHA 2019. *Mediastinal mass ratio of 0.33 or size of any single node/nodal mass ≥10 cm in diameter; ‡All received ≥2 prior regimens.
Event, n (%) N=70 Grade ≥3 TEAE 21 (30) Serious TEAE 12* (17.1) TEAE leading to treatment discontinuation 4† (5.7) TEAE leading to death 0 (0.0) Immune-related (ir) TEAEs (by aggregate category) ≥1 irTEAE 27 (36.8) Thyroid disorder 16 (22.9) Pneumonitis 5 (7.1) Skin adverse reactions 6 (8.6) Myositis/rhabdomyolysis/cardiomyopathy‡ 1 (1.4) Nephritis and renal dysfunction 1 (1.4) Other immune-related reactions (lipase increased 1 (1.4) 60 Summary of Tislelizumab Adverse Events cHL pivotal trial Source: Song et al., EHA 2019; Data cut: 11.26.18; TEAE, treatment-emergent adverse events by individual preferred term. *SAEs in 11 of the 12 patients determined to be possibly related to tislelizumab †Pneumonitis (n=2), focal segmental glomerulosclerosis (n=1), organizing pneumonia (n=1); ‡Blood creatine phosphokinase increased. TEAEs in ≥10% of Patients and Grade ≥3 TEAEs in ≥2 Patients Regardless of Causality Summary of Treatment-Emergent Adverse Events 0% 10% 20% 30% 40% 50% 60% 1 2 3 4 5 6 7 8 9 10 11 12 13 Patients (%) Series1 Series2
UC Enrolled Patients/evaluable N=113/104 Median Follow-up 8 months ORR 23.1% CR 7.7% PR 15.4% PFS median (95% CI) 2.1 (2.00, 2.46) OS median (95% CI) 9.8 months (7.46, 13.50) 61 Tislelizumab China UC Pivotal Trial Data Activity in previously treated patients Source: Ye et al., ESMO 2019 • IRC assessed • Per the investigator, treatment-related AEs (TRAEs) were reported in 93% (n=105/113) of patients with PD-L1+ UC. A total of 12 (11%) patients experienced a TRAE that led to treatment discontinuation. Drug eruption (n=2) was the only TRAE that led to treatment discontinuation in >1 patient. • Anemia (27%), decreased appetite (19%), and pyrexia (17%) were the only TRAEs occurring in >15% of patients; the majority of reported TRAEs were grade ≤2 in severity. Anemia (7%) was the only grade 3-4 TRAE occurring in ≥5% patients. • A total of 64% of patients experienced an immune-related TEAE. Common immune-related TEAEs included immune-mediated skin adverse reaction (n=38; 34%), immune-mediated hepatitis (n=27; 24%), thyroid disorders (n=15; 13%), and immune-mediated nephritis and renal dysfunction (n=13; 12%). No immune-related TEAEs ≥ grade 3 occurred in over 5% of patients. • Four patients experienced a fatal TRAE (hepatic failure, n=2; respiratory arrest, n=1; renal impairment, n=1). The events of hepatic failure and respiratory arrest were reported as possibly related by the investigator; the event of renal impairment was reported as possibly unrelated by the investigator.
62 Tislelizumab Response Data in Disease-Specific Cohorts Sources:1. Ph1A/1B data as of 08.31.18, ESMO Immuno-Oncology 2018 Congress (Sanjeev et al); 2. Ph1 data as of 06.08.17, ESMO 2017 Congress (Horvath et al, Abstract 389P); 3. Ph1 data as of 06.08.17, ESMO 2017 Congress (Meniawy et al, Abstract 388P); 4. Ph2 data as of 02.28.19, ESMO 2019 Congress (Ye et al); 5. Ph1 data as of 05.11.18, CSCO 2018; 6. Ph1/2 as of 12.01.18, ASCO 2019 (Wang et al); 7. Ph1/2 as of 05.20.19, WCLC 2019 (Barlow et al); 8. Ph2 as of 03.31.19, CSCO 2019 (Xu et al); * At time of data cutoff. Tumor Type Gastric Cancer Esophageal Cancer Esophageal Cancer Head & Neck SCC Ovarian Cancer HCC Urothelial Cancer NSCLC MSI-H / dMMR NPC Source ESMO-IO 20181 ESMO-IO 20181 CSCO 20198 ESMO 20172 ESMO 20173 ESMO-IO 20181 ESMO 20194 WCLC 20197 CSCO 20185 ASCO 20196 Median Treatment Duration -- -- -- 104 days (30-339) 71 days (29-540) -- -- -- 2.2 mo (0.69-11.1) 7.5 mo (2.1-15.8) Median Follow-up Time 4.9 mo (0.9-25.4) 5.2 mo (0.2-22.7) 13.0 mo (12.3-14.0) -- -- 10.8 mo (0.7-31.6) 7.6 mo (0.4-17.4) 11.2 mo (0.5-34.5) 4.4 mo (0.1-10.7) 11.7 mo (4.9-15.7) Median Duration of Response 8.5 mo NR 12.8 mo -- -- 15.7 mo 18.7 mo (6.2-18.7) NR -- 8.3 mo Evaluable Patients N=54 N=54 N=15 N=17 N=50 N=49 N=104 N=46 N=14 N=21 CR (Confirmed) -- 1 -- -- -- -- 8 -- -- -- PR 7 5 7 3 2 6 16 6 4 9 SD 9 14 5 6 20 19 14 23 4 9 Patients Remaining on Treatment* 3 3 4 3 6 5 30 7 9 9 Objective responses observed with limited follow-up in multiple disease-specific cohorts. NR = Not reached
63 China Label: Summary of Adverse Reactions Occurring in ≥5% of Patients in Phase 2 cHL Study1 1. Adverse reactions in this package insert are defined as: adverse events that assessed by investigator as related, definitely related, probably related, possibly related, unlikely related or missing causal relationship. Only adverse events that are assessed by investigator as definitely unrelated are excluded. The cutoff date of the data is 11.26.18. † Preferred term is based on ICH MedDRA Chinese version 20.0. * Severity of adverse reactions per NCI CTCAE v4.03. ** No Grade 5 adverse event was reported in this study. a. Fatigue is a composite term which includes fatigue, asthenia, and malaise. b. Pruritus is a composite term which includes pruritus and urticaria. c. Rash is a composite term which includes G1-2 rash, dermatitis and eczema. d. Pneumonitis is a composite term which includes pneumonitis, interstitial lung disease and organizing pneumonia. e. Musculoskeletal pain is a composite term which includes back pain, neck pain and musculoskeletal chest pain and spinal pain. Tislelizumab 200mg every 3 weeks n=70 Preferred term† All grades*, n(%) ≥Grade3**, n(%) General disorders and administration site conditions Pyrexia 38 (54.3) 0 (0.0) Fatiguea 7 (10.0) 0 (0.0) Chills 4 (5.7) 0 (0.0) Endocrine disorders Hypothyroidism 23 (32.9) 0 (0.0) Investigations Weight increased 19 (27.1) 2 (2.9) Weight decreased 6 (8.6) 0 (0.0) Skin and subcutaneous tissue disorders Pruritiusb 12 (17.1) 0 (0.0) Rashc 10 (14.3) 0 (0.0) Infections and infestations Upper respiratory tract infection 12 (17.1) 0 (0.0) Tislelizumab 200mg every 3 weeks n=70 Preferred term All grades*, n(%) ≥Grade3**, n(%) Respiratory, thoracic and mediastinal disorders Cough 8 (11.4) 0 (0.0) Pneumonitisd 4 (5.7) 3 (4.3) Metabolism and nutritional disorders Hyperlipidemia 5 (7.1) 0 (0.0) Hyperuricemia 4 (5.7) 0 (0.0) Musculoskeletal and connective tissue disorders Musculoskeletal paine 5 (7.1) 1 (1.4) Pain in extremity 5 (7.1) 0 (0.0) Gastrointestinal disorders Diarrhea 4 (5.7) 0 (0.0) Blood and lymphatic system disorders Anemia 4 (5.7) 0 (0.0) Nervous System disorders Headache 4 (5.7) 0 (0.0)
64 Tislelizumab Phase 1 Common AEs in ≥ 10% of Patients Source: BGB-A317 IB v6.0; All grades, regardless of causality; Data cut-off 27 April 2018; 6 months after Last Patient Enrolled; Of the 451 total patients in the Safety Population for Study BGB A317_001, 203 (45.0%) experienced at least 1 Grade 3 or higher TEAE. The most commonly occurring Grade 3 or higher TEAEs (≥ 2%; 9 or more patients overall incidence) were pneumonia (22 patients, 4.9%), anemia (18 patients, 3.2%), and hypokalemia (9 patients, 2.0%). 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 appetite 19 (4.2) 71 (15.7) 90 (20.0) Diarrhea 32 (7.1) 49 (10.9) 81 (18.0) Constipation 26 (5.8) 50 (11.1) 76 (16.9) Abdominal pain 26 (5.8) 38 (8.4) 64 (14.2) Vomiting 20 (4.4) 43 (9.5) 63 (14.0) Back pain 22 (4.9) 40 (8.9) 62 (13.7) Cough 15 (3.3) 45 (10.0) 60 (13.3) Rash 23 (5.1) 37 (8.2) 60 (13.3) Dyspnea 12 (2.7) 33 (7.3) 45 (10.0)
65 Tislelizumab Chemotherapy Combination Data in Lung Cancers Source: Wang et. al., CSCO 2019; Sq: squamous; SCLC: small cell lung cancer. Median follow-up 15.3 months. * Median PFS data cutoff 06.30.19. Treatment-emergent adverse events (TEAEs) occurred in all 54 patients; adverse events (AEs) reported as related to tislelizumab occurred in 46 patients (85.2%), and seven patients (13%) discontinued tislelizumab treatment due to AEs; Grade ≥3 TEAEs occurred in 43 patients, with the most common being decreased neutrophil count (48.1%), anemia (18.5%), decreased white blood cell count (13%), decreased platelet count (13%), thrombocytopenia (11.1%), neutropenia (7.4%), and increased alanine aminotransferase (ALT; 5.6%). A total of 14 patients (25.9%) experienced at least one immune-related adverse event (irAE), with the most common being thyroid disorders (16.7%), immune-mediated pneumonitis (7.4%), and immune-mediated hepatitis (3.7%); The most common TEAEs of any grade reported to be related to tislelizumab included asthenia (18.5%); hypothyroidism (13%); decreased appetite (11.1%); increased ALT (11.1%); and increased aspartate aminotransferase (AST; 11.1%); and fourteen patients (25.9%) experienced at least one serious TEAE; one patient with squamous NSCLC (cohort A) had a fatal AE of immune-mediated myositis/rhabdomyolysis/cardiomyopathy after one dose of tislelizumab. 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) Best Overall Response, n (%) CR 0 0 0 0 0 PR 7 (43.8) 12 (80.0) 4 (66.7) 13 (76.5) 36 (66.7) SD 8 (50.0) 2 (13.3) 1 (16.7) 2 (11.8) 13 (24.0) PD 1 (6.3) 0 0 1 (5.9) 2 (3.7) Missing 0 1 (6.7) 1 (16.7) 1 (5.9) 3 (5.6) ORR confirmed % 43.8 80.0 66.7 76.5 66.7 Median PFS, months* 9.0 7.0 NR 6.9 OS, months NR NR NR 15.6
66 Overview of Pamiparib (BGB-290) Selective Inhibitor of PARP1 and PARP2 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 of hematological toxicities (e.g. thrombocytopenia), no liver toxicity DEVELOPMENT PLAN • Priority review granted by NMPA in patients with gBRCA+ ovarian cancer • Two ongoing global Ph1b/2 trials with chemotherapy: combination with radiation therapy and temozolomide (TMZ) in glioblastoma or combination with TMZ in advanced solid tumors • Enrollment complete in Ph3 trial in China as maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer • Enrolling patients for a global Ph2 trial in gastric cancer as maintenance therapy • Internal combination with tislelizumab: preliminary anti-tumor activity observed in multiple solid tumors MILESTONES AND STATUS • NMPA filing in ovarian cancer accepted for priority review 07.27.20 • Presented Ph 1/2 data in advanced ovarian cancer at ESMO 2020 1 As of October 16, 2020.
67 Pamiparib Clinical Program *Some indications will not require a non-pivotal Ph2 clinical trial prior to beginning pivotal Ph2 or 3 clinical trials. **Confirmatory clinical trials post-approval are required for accelerated approvals. PROGRAM (TARGET) DOSE ESCALATION DOSE EXPANSION PIVOTAL FILED PH1a PH1b PH2* PH2** PH3 pamiparib (BGB-290, PARP) 3L gBRCA+ OC (Announced priority review granted by NMPA July 27, 2020) 2L platinum-sensitive OC maintenance HER2- BRCA mutated breast cancer 1L platinum-sensitive GC maintenance Solid tumors + TMZ (Chemo) Solid tumors + RT/TMZ (RT/Chemo) Solid tumors + tislelizumab (PD-1) Solid tumors • Two ongoing global Ph1b/2 trials with chemotherapy: combination with radiation therapy and temozolomide (TMZ) in glioblastoma or combination with TMZ in advanced solid tumors • Internal combination with tislelizumab: preliminary anti-tumor activity observed in multiple solid tumors Global China
68 Pamiparib Phase 2 in Advanced Ovarian Cancer Patients were considered efficacy-evaluable if they had measurable disease at baseline per RECIST v1.1 and had ≥1 postbaseline tumor assessment, unless treatment had been discontinued due to clinical progression or death prior to tumor assessment. Abbreviations: BOR, best overall response; CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DCR, disease control rate; IRC, independent review committee; NE, not estimable; ORR, objective response rate; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. *CBR=CR+PR+SD ≥24 weeks; DCR=CR+PR+SD; ORR=CR+PR. Platinum Sensitive Ovarian Cancer (n=82) Platinum Resistant Ovarian Cancer (n=19) BOR, n (%) CR 8 (9.8) 0 (0.0) PR 45 (54.9) 6 (31.6) SD 25 (30.5) 12 (63.2) PD 4 (4.9) 1 (5.3) NE 0(0.0) 0 (0.0) ORR, % (95% CI) 64.6 (53.3 - 74.9) 31.6 (12.6 – 56.6) DCR, % (95% CI) 95.1 (88.0 - 98.7) 94.7 (74.0 – 99.9) CBR ≥24wks*, % (95% CI) 74.4 (63.6 - 83.4) 52.6 (28.9 – 75.6) Median time to response, months (min, max) 1.7 (1.3, 6.3) 1.4 (1.2, 1.4) Tumor Response in the Efficacy-Evaluable Population by IRC based on RECIST v1.1 Best Change in Sum of Target Lesion Diameters by Confirmed Best Overall Response of the Efficacy- Evaluable Population per RECIST v1.1
69 Pamiparib Phase 2 in Advanced Ovarian Cancer Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; PA, protocol amendment; PSOC, platinum-sensitive ovarian cancer. Preferred Term, n (%) Platinum Sensitive Ovarian Cancer (n=90) Platinum Resistant Ovarian Cancer (n=23) All Grades Grade ≥3 All Grades Grade ≥3 Anemia 80 (88.9) 34 (37.8) 21 (91.3) 13 (56.5) Nausea 61 (67.8) 1 (1.1) 16 (69.6) 0 (0.0) Decreased Neutrophil count 56 (62.2) 28 (31.1) 13 (56.5) 10 (43.5) Decreased white blood cell count 54 (60.0) 17 (18.9) 14 (60.9) 5 (21.7) Vomiting 46 (51.1) 4 (4.4) 11 (47.8) 1 (4.3) Decreased platelet count 25 (27.8) 4 (4.4) 10 (43.5) 1 (4.3) Decreased appetite 29 (32.2) 0 (0.0) 5 (21.7) 0 (0.0) Asthenia 26 (28.9) 1 (1.1) 6 (26.1) 0 (0.0) Diarrhea 19 (21.1) 3 (3.3) 6 (26.1) 0 (0.0) Increased AST 20 (22.2) 0 (0.0) 4 (17.4) 1 (4.3) Decreased lymphocyte count 19 (21.1) 6 (6.7) 5 (21.7) 2 (8.7) Increased ALT 18 (20.0) 1 (1.1) 5 (21.7) 0 (0.0) Leukopenia 20 (22.2) 9 (10.0) 3 (13.0) 3 (13.0) Pamiparib was generally tolerated, consistent in patients with PSOC and PROC, and similar to other PARP inhibitors; Across the trial, the most common (≥20.0%) TEAEs of any grade included anemia (89.4%), nausea (68.1%), decreased neutrophil count (61.1%), decreased white blood cell count (60.2%), vomiting (50.4%), decreased platelet count (31.0%), decreased appetite (30.1%), asthenia (28.3%), diarrhea (22.1%), increased AST (21.2%), decreased lymphocyte count (21.2%), increased ALT (20.4%), and leukopenia (20.4%); Across the trial, the most common (≥10.0%) Grade ≥3 TEAEs included anemia (41.6%), decreased neutrophil count (33.6%), decreased white blood cell count (19.5%), and leukopenia (10.6%); And no myelodysplastic syndrome or significant complications potentially related to hematologic AEs, such as Grade ≥3 hemorrhage, fever, or infection, were reported in the trial. Treatment-Emergent Adverse Events of Any Grade (≥20% in the Total Population) and of Grade ≥3