Document

______________________________________________________________________________________________________
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): June 18, 2019

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*
 
6160
 
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. [   ]
______________________________________________________________________________________________________









Item 7.01. Regulation FD Disclosure.

BeiGene, Ltd. (the “Company” or “BeiGene”) hosted an investor conference call and webcast of mid-2019 clinical data updates on June 20, 2019. 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. The information in Item 7.01 of this Current Report on Form 8-K, including the presentation, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing or this Current Report.

Item 8.01. Other Events.

On June 18, 2019, the Company issued a joint press release with SpringWorks Therapeutics, Inc. (“SpringWorks”) announcing the formation of MapKure, LLC (“MapKure”), a newly created entity that is jointly owned by the Company and SpringWorks. MapKure intends to develop BGB-3245, an investigational, oral, selective small molecule inhibitor of monomer and dimer forms of activating B-RAF mutations including V600 BRAF mutations, non-V600 B-RAF mutations, and RAF fusions. These mutations and fusions have been identified in a number of solid tumors to be drivers of cancer growth, including in non-small cell lung cancer, colorectal cancer, thyroid cancer, and brain tumors. BGB-3245 was discovered by BeiGene scientists and is currently in preclinical development. Under the terms of the agreements, SpringWorks has made an equity investment into MapKure and BeiGene has contributed an exclusive royalty and milestone-bearing license to develop and commercialize BGB-3245 outside of Asia, but including rights to Japan, in exchange for a majority ownership position in MapKure. MapKure will form a joint steering committee that will oversee clinical development and operations for BGB-3245, as well as a Board of Directors. Both the joint steering committee and the Board will include members from BeiGene, SpringWorks and MapKure’s CEO. Further terms of the agreements were not disclosed. The full text of this press release is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

On June 19, 2019, the Company issued a press release announcing the results from two ongoing clinical studies of its investigational BTK inhibitor zanubrutinib in patients with mantle cell lymphoma (MCL) in two presentations at the 15th International Conference on Malignant Lymphoma (ICML), taking place June 18-22, 2019 in Lugano, Switzerland. The full text of this press release is filed as Exhibit 99.3 to this Current Report on Form 8-K and is incorporated herein by reference.

On June 20, 2019, the Company issued a press release announcing results from an ongoing pivotal Phase 2 clinical study of its investigational BTK inhibitor zanubrutinib being conducted in China in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in an oral presentation at the ICML. The full text of this press release is filed as Exhibit 99.4 to this Current Report on Form 8-K and is incorporated herein by reference.

On June 20, 2019, the Company issued a press release announcing results from an ongoing Phase 1b clinical study of its investigational BTK inhibitor zanubrutinib in combination with GAZYVA® (obinutuzumab) in patients with R/R or treatment naïve CLL or SLL, and patients with R/R follicular lymphoma (FL). These data were included in an oral presentation at the ICML. The full text of this press release is filed as Exhibit 99.5 to this Current Report on Form 8-K and is incorporated herein by reference.

In connection with the conference call and webcast described above under Item 7.01, the Company provided an update on the enrollment status of tislelizumab’s development programs as set forth on Page 7 of Exhibit 99.1, which is incorporated herein by reference.





Item 9.01. Financial Statements and Exhibits.
 
(d) Exhibits.
 
 
 
 
Exhibit No.
 
Description
99.1
 
Company Presentation titled “BeiGene Mid-Year 2019 Clinical Data Wrap-Up,” dated June 20, 2019
 
 
 
99.2
 
Press Release titled “BeiGene and SpringWorks Therapeutics Announce the Formation of MapKure to Develop BGB-3245, an Investigational, Selective Next-Generation RAF Kinase Inhibitor,” issued on June 18, 2019
 
 
 
99.3
 
Press Release titled “BeiGene Announces Updated Results from Two Ongoing Clinical Trials of Zanubrutinib in Patients with Mantle Cell Lymphoma in Presentations at the 15th International Conference on Malignant Lymphoma (ICML),” issued on June 19, 2019
 
 
 
99.4
 
Press Release titled “BeiGene Presents Pivotal Phase 2 Clinical Results of Zanubrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma at the 15th International Conference on Malignant Lymphoma (ICML),” issued on June 20, 2019
 
 
 
99.5
 
Press Release titled “BeiGene Announces Phase 1b Clinical Results of Zanubrutinib in Combination with GAZYVA® (Obinutuzumab) in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Follicular Lymphoma at the 15th International Conference on Malignant Lymphoma (ICML),” issued on June 20, 2019
 











Exhibit Index
 
 
 
 
Exhibit No.
 
Description
99.1
 
 
 
 
99.2
 
 
 
 
99.3
 
 
 
 
99.4
 
 
 
 
99.5
 
 
 
 
 







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: June 20, 2019
By:
/s/ Scott A. Samuels
 
Name:
Scott A. Samuels
 
Title:
Senior Vice President, General Counsel


 

a991bgnemid19confwrapup2
Exhibit 99.1 BeiGene Mid-Year 2019 Clinical Data Wrap-Up June 20, 2019


 
Welcome Howard Liang, Ph.D., CFO and Chief Strategy Officer 2


 
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. Disclosures Examples of such forward-looking statements include those regarding investigational drug candidates and clinical trials and the status and related results thereto, as well as those regarding continuing and further development and commercialization efforts and transactions with third parties. Such statements, based as they are on the current analysis and expectations of management, inherently involve numerous risks and uncertainties, known and unknown, many of which are beyond BeiGene’s control. Such risks include but are not limited to: the impact of general economic conditions, general conditions in the pharmaceutical industries, changes in the global and regional regulatory environments in the jurisdictions in which BeiGene does business, market volatility, fluctuations in costs and changes to the competitive environment. Consequently, actual future results may differ materially from the anticipated results expressed in the forward-looking statements. In the case of forward- looking statements regarding investigational drug candidates and continuing further development efforts, specific risks which could cause actual results to differ materially from BeiGene’s current analysis and expectations include: failure to demonstrate the safety, tolerability and efficacy of our drug candidates, final and quality controlled verification of data and the related analyses, the expense and uncertainty of obtaining regulatory approval, including from the FDA, NMPA (formerly CFDA/CDA) and EMA, the possibility of having to conduct additional clinical trials and BeiGene’s reliance on third parties to conduct drug development, manufacturing and other services. Further, even if regulatory approval is obtained, pharmaceutical products are generally subject to stringent on-going governmental regulation, challenges in gaining market acceptance and competition. These statements are also subject to a number of material risks and uncertainties that are described in BeiGene’s filings with the Securities and Exchange Commission (SEC). The reader should not place undue reliance on any forward-looking statements included in this presentation or in the accompanying oral presentation. These statements speak only as of the date made, and BeiGene is under no obligation and disavows any obligation to update or revise such statements as a result of any event, circumstances or otherwise, unless required by applicable legislation or regulation. Some of the clinical data in this presentation relating to BeiGene’s investigational drug candidates is from early phase, single-arm 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. BeiGene is still conducting 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 contains 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


 
Agenda Welcome – Howard Liang, Ph.D. Introduction – John V. Oyler Zanubrutinib – Jane Huang, M.D. • Pooled safety data summary • Phase 3 in WM: MYD88WT cohort • Phase 2 in R/R CLL/SLL • Phase 1 in WM cohort • Phase 1 in MCL cohort • Phase 2 in R/R MCL summary • Phase 1b Combination with Obinutuzumab in R/R FL and CLL Tislelizumab – Eric Hedrick, M.D. • Phase 2 in R/R cHL • Phase 1 NPC cohort Key Takeaways – Eric Hedrick, M.D. Q&A 4


 
Introduction John V. Oyler, Chairman, Co-Founder and CEO 5


 
Business Updates Regaining tislelizumab worldwide rights • Termination of collaboration agreement with Celgene ahead of pending BMS-Celgene merger • BeiGene to receive $150M payment from Celgene • Early resolution in the best interest of the asset and both companies • Minimal interruption in clinical execution – BeiGene has been leading 90% of the Phase 3 or potentially registration- enabling trials for tislelizumab • Full options available commercially, from going alone, to co-promotion, to out-licensing – we will seek to maximize the value of the asset Regulatory progress • Tislelizumab and zanubrutinib approvals in China expected in 2019 • Tislelizumab filed for urothelial carcinoma in China in May • ABRAXANE® filed for pancreatic cancer in China in May Clinical progress • Executing towards enrollment completion in 2019 for a large number of Phase 3 or potentially registration-enabling trials • Progress will be updated in quarterly earnings releases • Expect data readouts in 2019 / 2020 from a large number of key Phase 3 or potentially registration-enabling studies for zanubrutinib, tislelizumab and pamiparib 6


 
Tislelizumab’s Advanced Development Status Phase 3 (n=800) in 2L NSCLC Enrollment complete tislelizumab vs. docetaxel NSCLC Primary endpoint: OS Initiated in Nov. 2017 Enrollment expected to complete in 2019 Phase 3 (n=640) in 1L HCC Phase 2 (n=225) in 2L/3L HCC tislelizumab vs. sorafenib tislelizumab monotherapy Enrollment expected to complete in 2020-2021 Global HCC Primary endpoint: OS Primary endpoint: ORR by IRC Trials Initiated in Jan. 2018 Initiated in Apr. 2018, enrollment completed in 1Q:19 (China and Phase 3 (n=450) in 2L ESCC Phase 3 (n=480) in 1L advanced ESCC ROW) tislelizumab vs. single-agent chemo (paclitaxel, docetaxel, or irinotecan) tislelizumab or placebo + platinum- and fluoropyrimidine-based chemo ESCC Primary endpoint: OS Co-primary endpoints: PFS and OS Initiated in Jan. 2018 Initiated in Dec. 2018 Phase 3 (n=720) in 1L advanced GC R/R NK/T- Phase 2 (n=90) in 1L R/R Mature T- and NK- Neoplasms tislelizumab or placebo + platinum- and fluoropyrimidine-based chemo cell tislelizumab monotherapy GC Co-primary endpoints: PFS and OS lymphom Primary endpoints: ORR Initiated in Dec. 2018 as Initiated in Apr. 2018 Phase 3 (n=340) in 1L Stage IIIB or IV squamous NSCLC Phase 3 (n=320) in 1L Stage IIIB or IV non-squamous N SC LC Tislelizumab+ paclitaxel and carboplatin combo or nab-paclitaxel and Tislelizumab+ chemo (platinum-pemetrexed) vs. chemo carboplatin combo vs. paclitaxel and carboplatin combo NSCLC Primary endpoint: PFS 2,714 patients Primary endpoint: PFS Initiated in Jul. 2018 Initiated in Aug. 2018 currently enrolled Pivotal phase 2 (n=110) in 2L UC Pivotal phase 2 (n=70) in R/R cHL in these trials tislelizumab monotherapy China tislelizumab monotherapy UC Primary endpoint: ORR cHL Primary endpoint: ORR Trials 2,950 total Initiated in Jul. 2017, enrollment completed in 3Q:18, Initiated in Apr. 2017, enrollment completed in NDA accepted May 2019 4Q:17, NDA accepted in Aug 2018 patients dosed MSI-H or Phase 2 (n=60) in MSI-H or dMMR solid tumors across all Phase 3 (n=256) in 1L tislelizumab + chemo (gemcitabine dMMR tislelizumab monotherapy plus cisplatin) vs. placebo + chemo Primary endpoint: PFS tislelizumab solid Primary endpoint: ORR NPC Initiated in Apr. 2019 tumors Initiated in Sept. 2018 studies *Tislelizumab dosage 200mg every three weeks, Q3W. Global Ph3 trial in Stage III NSCLC is run by Celgene; 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. ORR: Overall response rate; PFS: Progression-free survival; cCRT: concurrent chemoradiotherapy; IRC: Independent Review Committee; ITT: Intent-to-treat 7


 
Zanubrutinib Jane Huang, M.D., CMO, Hematology


 
Zanubrutinib Pooled Safety Abstract PS1159 24th European Hematology Association Congress Jane Huang, M.D., CMO, Hematology 9


 
Zanubrutinib Monotherapy Studies Pooled Safety Data (n=682) M ost Common AEs (All Grade in ≥10% or Grade 3 or Higher in ≥ 3%) AEs of Interest by Category % of patients with ≥ 1 AE of interest Infections Bleeding (petechiae/contusion/hemorrhage)* Neutropenia Thrombocytopenia Anemia Grade 1-2 Hypertension Grade ≥3 2nd primary malignancy** Skin cancers Opportunistic infections Major hemorrhage^ Atrial fibrillation/flutter 0% 20% 40% 60% 80% 100% Median exposure 13.4 months. * Inclusive of major hemorrhage; events consist primarily of grade 1-2 mucocutaneous bleeding. ** Inclusive of skin cancers (primarily basal cell [3.5%] and squamous cell carcinomas [2.2%]). ^ Includes any serious or grade ≥3 bleeding event or central nervous system bleed of any severity grade 10


 
Pooled Safety Data* Zanubrutinib Zanubrutinib Acalabrutinib6 Ibrutinib Background EHA 20181 EHA 20192 Rate n 476 682 612 7565; 1,124b; 2,0904-2,1523 1,605c Major hemorrhage % 2% 2.5% 2.8% 4%5 (Gr≥3) (2%) (2.1%) (2.0%) 3%5 [events/100 pt. yrs.] [2.07] - [3.03] [1.93] Atrial fibrillation % ~2% 1.9% 2.9% 9%c (Gr≥3) (0.2%) (0.6%) (1.0%) (4.1%)c [events/100 pt. yrs.] [1.56] - [3.34] [0.844] Diarrhea ~15% 19.4% 40% 39%c (Gr≥3) (1%) (0.9%) (2.1%) (3%)c Median exposure, mo 7.0 (0.02-36.05) 13.4 (6.1-19.6) 18.5 (0.03- 14.8moca (25th-75th percentile) 37.4)# (range)# * Pooled safety data from separate trials and sources. Limitations regarding cross-trial comparisons apply. Sources: 1 Tam et al, EHA 2018; 2 Tam et al, EHA 2019; 3 Caron, F Blood Advances 1:12 2019; 4 Leong, D Blood 128:1 2016; 5 O’Brien S Clin Lymphoma Myeloma & Leukemia 18:10 2018; 6 Byrd et al, ASH 2017; a Median treatment duration; b Data from label out of 1,124 patients; c Data from label out of 1,605 patients 11


 
Zanubrutinib Phase 3 in WM: MYD88WT Cohort Abstract PF487 24th European Hematology Association Congress Jane Huang, M.D., CMO, Hematology 12


 
WT Trial Design: Phase 3 in WM, MYD88 Cohort Data cut: Feb 28, 2019 Ar m A Cohort 1: R/R or TN* WM with MYD88L265P Mutation Zanubrutinib 160 mg bid until PD MYD88MUT WM patients R (n=201) 1:1 Ar m B Ibrutinib Stratification factors: 420mg qd until PD • CXCR4 mutational status (CXCR4WHIM vs CXCR4WT or missing) • No. of prior lines of therapy (0 vs 1-3 vs > 3) Cohort 2: WM with wild type MYD88; present in ~10% of enrolled patients Ar m C MYD88WT WM patients Zanubrutinib (n = 26 WT + 2 unknown) 160 mg bid until PD bid, twice daily ; PD, progressive disease; qd, once daily; R/R, relapsed/refractory; TN, treatment-naïve; *TN must be unsuitablefor standard chemoimmunotherapy. EUDRACT 2016-002980-33; NCT03053440 13


 
Patient and Disease Characteristics Data cut: Feb 28, 2019 Characteristic Total (n=26) Age, years, median (range) 71.5 (39-87) Gender, n (%) Male 14 (53.8) Female 12 (46.2) ECOG performance status, n (%) 0 9 (34.6) 1 14 (53.8) 2 3 (11.5) Prior treatment status Treatment-naïve, n (%) 5 (19.2) Relapsed/refractory (R/R), n (%) 21 (80.8) Number of prior therapies for R/R patients, median (range) 1 (1-5) Extramedullary Disease present at baseline 13 (50.0) Genotype, n (%) MYD88WT/CXCR4WT 23 (88.5) MYD88WT/CXCR4WHIM 1 (3.8) MYD88WT/CXCR4 unknown 2 (7.7) ECOG, Eastern Cooperative Oncology Group. 14


 
Best Response Data cut: Feb 28, 2019 Total Best response, n (%) (n=26) Overall response rate (ORR) 21 (80.8) Major response rate (MRR, PR or better) 14 (53.8) VGPR 6 (23.1)a,b PR 8 (30.8)b MR 7 (26.9) SD 4 (15.4) PD 1 (3.8) Time to MR, med (range), mo Months 2.9 (1.9 -7.4) Study follow-up time, med (range), mo Months 12.2 (2.3 - 21.7) aOne patient achieved IgM complete response (normalized IgM and negative immunofixation since Cycle 11, with bulky extramedullary disease improving). bIncluding pts confirmed by next-generation sequencing of no other activating MYD88 mutations: 3 of 6 VGPR (including IgM CR); 3 of 8 PR. CR, complete response; MR, minor response; PD, progressive disease; PR, partial response; SD, stable disease; VGPR, very good partial response. 15


 
Adverse Events Overview Data cut: Feb 28, 2019 Treatment Emergent Adverse Event n (%) 2 patients discontinued due to AEs Patients w ith ≥1 AE grade ≥3 12 (46.2) • Grade 4 subdural hemorrhage Patients w ith ≥1 serious AE 8 (30.8) • Grade 3 diarrhea a AE leading to treatment discontinuation 2 (7.7) Major hemorrhage occurred in 2 Fatal AE 0 patients • Gastric ulcer hemorrhage AE of interest (BTK inhibitor class) • Periorbital hematoma, subdural Bleeding/petechiae/bruis ing of any grade 9 (34.6) hematoma, and subdural Most commonly grade 1 contusion 4 (15.4) hemorrhage; treatment was Diarrhea 5 (19.2) permanently discontinued per Hypertension 5 (19.2) protocol Grade 3 or 4 cytopenia 4 (15.4) No fatal treatment emergent AEs or Grade 3 or 4 infections 3 (11.5) atrial fibrillation/flutter events have Second malignancyb 3 (11.5) been reported Major hemorrhagec 2 (7.7) Atrial fibrillation/flutter 0 Common adverse events (> 15% of patients) include, all grades (Gr≥3): hypertension 19.2%(11.5%), diarrhea 19.2%(7.7%), pneumonia 15.4%(3.8%), upper respiratory tract infection 15.4%, muscle spasm 15.4%, contusion 15.4%, constipation 15.4% AE, adv erse event; SAE, serious adverse event. aGrade 4 subdural hemorrhage (related) and grade 3 diarrhea (related). bBasal cell carcinoma (n=2) and Queyrat erythroplasia (n=1). cDefined as any-grade ≥3 hemorrhage or any-grade CNS hemorrhage: gastric ulcer hemorrhage; 1 patient had periorbital hematoma, subdural hematoma, and subdural hemorrhage. 16


 
Zanubrutinib Cohort 2 MYD88WT Results Consistent with Phase 1 Data cut: Feb 28, 2019 Be st re sponse , Phase 3 cohort 2 Phase 11 n (%) (n=26) (n=8) EHA 2019 ORR 21 (80.8) 7(87.5) MRR 14 (53.8) 5(62.5) CR / VGPR 6 (23.1)a,b 2(25.0) PR 8 (30.8) 3(37.5) MR 7 (26.9) 2(25.0) SD 4 (15.4) 1(12.5) PD 1 (3.8) 0 Study follow-up time, median (range) Months 12.2 (2.3 - 21.7) 24.3 (4.1-45.7)* 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 361 (46.8); AE leading to treatment discontinuation 82 (10.4); Fatal AE 5c (6.5). 1Includes 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). aOne patient achieved IgM complete response (normalized IgM and negative immunofixation since Cycle 11, with bulky extramedullary disease improving). bIncluding the patient who had CXCR4 frameshift mutation. 1 Tam et al, EHA 2019; 1 Safety summary below; * Follow up f or full WM cohort. 17


 
Zanubrutinib Phase 2 in R/R CLL/SLL in China (ICML) Abstract 015 15th International Conference on Malignant Lymphoma Jane Huang, M.D., CMO, Hematology 18


 
Trial Design: Phase 2 in R/R CLL/SLL in China R/R CLL/SLL Key Criteria Zanubrutinib 160 mg bid Inclusion Criteria until progression, intolerable toxicity, • ≥18 years old or end of study • At least one treatment indication • Measurable lesion Exclusion Criteria • Richter syndrome Objectives • Insufficient organ function • Primary: IRC-assessed ORR • Secondary: PFS, DOR, TTR, safety • Exploratory: Biomarkers Response assessment • iwCLL 2008 criteria for CLL (with modification for PRL (Cheson, Hallek 2012)) • CT-based assessment according to Lugano Classification for SLL1 bid, twice a day ; CLL, chronic lymphocytic leukemia; DOR, duration of response; IRC, independent review committee; PK, pharmacokinetics; SLL, small lymphocytic lymphoma; TTR, time to response. 1. Cheson BD et al. J Clin Oncol. 2014;32(27):3059-3067. 19


 
Patient and Disease Characteristics Data cut: Dec 14, 2018 Baseline Characteristics n = 91 Baseline Characteristics n = 91 Median age (range), years 61.0 (35 - 87) Splenomegaly, n (%) 56 (61.5) Male, n (%) 52 (57.1) Hepatomegaly, n (%) 11 (12.1) Late stage a, n (%) 63 (69.2) Absolute lymphocyte count, n (%) 9 57 (62.6) Prior therapy, n (%) <25 ×10 /L Alkylator (including bendamustine) 68 (74.7) 25 – 100 ×109/L 26 (28.6) Purine analog 52 (57.1) >100 × 109/L 8 (8.8) Anti-CD20 antibody 54 (59.3) Refractory to last therapy, n (%) 72 (79.1) Genetic Characteristics n = 91 ECOG PS 0/1, n (%) 88 (96.7) TP53 mutation and/or 17p deletion, n (%) 22 (24.2) Bulky disease, n (%) LDi ≥5 cm 40 (44.4) IGHV unmutated, n (%) 51 (56.0) Beta-2 microglobulin >3.5 mg/L, n (%) 68 (74.7) Cytogenetic abnormalities, n (%) 17p deletion 17 (18.7) 11q deletion 20 (22.0) 13q deletion 41 (45.1) Trisomy 12 21 (23.1) a Percentages are based on number of CLL patients with Binet C and SLL patients with stage III and IV. ECOG PS, Eastern Cooperative Oncology Group performance status. 20


 
Best Response Data cut: Dec 14, 2018 Response by IRC n = 91 ORR including PR-L, n (%) 77 (84.6) BOR, n (%) Complete response (CR) 3 (3.3) Partial response (PR) 54 (59.3) Partial response with lymphocytosis (PR-L) 20 (22.0) Stable disease (SD) 4 (4.4) Progressive disease (PD) 4 (4.4) Not evaluable a 3 (3.3) Discontinued prior to first post-baseline assessment 3 (3.3) The ORR was 91.2% (83.4, 96.1) and the PR or higher rate was 72.5% (62.2, 81.4) as assessed by investigators High concordance rate for overall response assessments was 91.2% between IRC and investigator assessments Median study follow-up 15.08 months aMissing anatomy imaging for 2 patients, and without evidence of response maintenance for at least 2 months for 1 patient, separately. BOR, best overall response. 21


 
Progression-Free Survival Data cut: Dec 14, 2018 100 The median follow-up 90 time for PFS was 12.9 80 92.2% at 6 months months (0.8, 20.4) (95% CI: 84.3, 96.2) 87.2% at 12 months 70 Median PFS has (95% CI: 78.0, 92.7) not been reached 60 50 40 30 20 10 + Censored Progression - Free Survival Probability 95% CI 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Months After First Dose Number of Subjects at Risk 91 90 88 84 83 83 81 81 81 80 80 76 56 38 38 19 19 8 7 2 2 0 CI, confidence interval; PFS, progression-free survival. 22


 
TEAE Regardless of Causality Data cut: Dec 14, 2018 Serious AEs were reported TEAE with Frequency ≥10% in 33% patients and grade ≥3    Neutrophil count decreased AEs were reported in 76%.    Upper respiratory tract infection    Purpura    Platelet count decreased There were 8 patients reported    Haematuria AEs leading to treatment    Anaemia    Hypokalaemia discontinuation    Cough    Hyperglycaemia Three patient-reported AEs    White blood cell count decreased leading to death, all within 30    Carbon dioxide increased    Diarrhoea days of last dose    Lung infection • Lung infection / cardiac failure /    Urinary tract infection respiratory (unlikely related)    R ash    Urobilinogen urine increased • Cardiopulmonary failure (unlikely    Alanine aminotransferase… related)    Hypoalbuminaemia    Hyperuricaemia ≥ Grade 3 All grades • MODS (not related) in the setting Aspartate aminotransferase… of disease progression Pyre xia • These were determined unlikely or 0 10 20 30 40 50 60 70 80 90 100 unrelated to zanubrutinib treatment Patients, % ALT, alanine aminotransferase; AST, aspartate aminotransferase; TEAE, treatment-emergent adverse event; MODS, multiple organ dysfunction syndrome 23


 
Ibrutinib in Chinese Patients with R/R CLL Ibrutinib Trial PCI-32765CLL3002* Arms Ibrutinib Rituximab Investigator Investigator n 107 53 mFU months 17.8 ORR% (w/o PR-L) 45% 5.6% ORR% (including lymphocytosis) 57% 5.6% CR 1.9% 0 PR 43% 5.6% PR-L 11% 0 AEs, n (%); Ibrutinib (n=86) All Grade (%) Grade 3 or 4 (%) Rituximab (n=42) All Grade (%) Grade 3 or 4 (%): Diarrhea 25 (29.1), 2 (2.3), 3 (7.1), 0; Nasopharyngitis 14 (16.3), 1 (1.2), 1 (2.4), 0; Pneumonia 22 (25.6), 17 (19.8), 7 (16.7), 4 (9.5); Upper respiratory tract infection 20 (23.3), 6 (7.0), 4 (9.5), 1 (2.4); Rash 20 (23.3), 1 (1.2), 4 (9 .5), 0; Cough 19 (22.1), 1 (1.2), 2 (4.8), 0; Thrombocytopenia 15 (17.4), 5 (5.8), 1 (2.4), 0; Leukocytosis 12 (14.0), 12 (14.0), 0, 0; Fatigue 13 (15.1), 0, 3 (7.1), 0; Musculoskeletal Pain 13 (15.1), 0, 0, 0; Lymphocyte count increased 10 (11.6), 8 (9.3), 0, 0; Lactate dehydrogenase increased 9 (10.5), 2 (2.3), 1 (2.4), 0; Vertigo 9 (10.5), 0, 0, 0; Neutrophil count decreased (62.8), (37.2), (54.8), (33.3); Platelet count decreased (65.1), (15.1), (45.2), (9.5); Hemoglobin decreased (46.5), (1.2), (26.2), (0). Source: *Ibrutinib Chinese label 24


 
Other Zanubrutinib Studies Jane Huang, M.D., CMO, Hematology 25


 
Updated WM Cohort Safety and Efficacy from Global Phase 1 (EHA) Data cut: Sep 16, 2018 Be st re sponse , All Efficacy TN Patients (n=24) R/R Patients (n=49) n (%) Evaluable (n=73) ORR 67 (92) 23 (96) 44 (90) CR 1(1) 0(0) 1(2) VGPR 30 (41) 7 (29) 23 (47) PR 29 (40) 14 (58) 15 (31) MR 7 (10) 2 (8) 5 (10) Study follow-up, 23.9 (4.4-45.7) 12.3 (5.9-28.0) 24.8 (4.4-45.7) median (range), mo Adverse Event Overview n (%) Event Patients with ≥1 AE Grade ≥3 40 (51.9) Patients with ≥1 serious AE 36a (46.8) AE leading to treatment discontinuation 8b (10.4) Fatal AE 5c (6.5) AE of special interest n(%): Petechiae/purpura/contusion 34 (44.2), Diarrhea 13 (16.9), Hypertension 9 (11.7), Major hemorrhage 2 (2.6), Atrial fibrillation/flutter 4 (5.2); Major hemorrhage defined as any grade ≥3 hemorrhage or any-grade central nervous system hemorrhage, gastrointestinal hemorrhage (n=1), grade 3 hemorrhagic cystitis (n=1). aIncludes 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. bAbdominal 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). cSeptic arthritis (patient also reported disease progression), worsening bronchiectasis, abdominal sepsis, gastric adenocarcinoma, and scedosporium infection (each n=1). 26


 
Updated MCL Cohort Safety and Efficacy from Global Phase 1 (ICML) Data cut: Dec 13, 2018 Be st re sponse , All Efficacy TN (n=11) R/R (n=37) n (%) Evaluable (n=48) Follow-up for efficacy-evaluable pts, 16.7 8.3 19.4 median (range), mo (1.6-38.2) (1.6-27.9) (1.9-38.2) ORR, n (%) 41 (85.4) 9 (81.8) 32 (86.5) CR, n (%) 14 (29.2) 3 (27.3) 11 (29.7) PR, n (%) 27 (56.3) 6 (54.5) 21 (56.8) Adverse Event Overview Overall (n=53) Event, n (%) Patients with ≥1 AE Grade ≥3 29 (54.7) Patients with ≥1 serious AE 20a (37.7) AE leading to treatment discontinuation 10b (18.9) Fatal AE 5c (9.4) The majority of pts were assessed via CT-scan; PET scan was optional, per trial protocol. Best overall response was upgraded in 3 patients based on PET assessment. aSAEs determined to be possibly related to zanubrutinib (n=4): grade 3 leukocytosis, grade 3 peripheral edema + grade 3 worsening back pain, grade 3 cellulitis, grade 3 subdural hematoma. bGrade 5 Cerebral inf arction, grade 5 pneumonia, grade 5 worsening congestive cardiac failure, grade 3 acute kidney injury + grade 3 ANCA vasculitis, grade 3 pneumonia, grade 3 peripheral edema (related), grade 4 myelodysplastic syndrome, grade 3 renal hematoma, grade 2 small cell lung cancer, grade 3 subdural hematoma (related) (each n=1). One additional patient was reported as progressive disease but also had grade 5 sepsis + grade 2 f ever. cCerebral infarction (n=1), pneumonia (n=1), worsening congestive cardiac failure (n=1), sepsis (n=2). All determined to be unrelated to study drug. 27


 
Updated Data from Zanubrutinib Phase 2 China Pivotal Study in R/R MCL (ICML) Data cut: Feb 15, 2019 Best response, n (%) Data cutoff Mar 2018 Data cutoff Feb n = 85a 15, 2019 n = 86 INV IRC INV ORR 72 (84.7) 71 (83.5) 72 (83.7) CR 62 (72.9) 50 (58.8) 67 (77.9) PR 10 (11.8) 21 (24.7) 5 (5.8) SD 1 (1.2) 2 (2.4) 1 (1.2) PD 8 (9.4) 6 (7.1) 8 (9.3) Discontinued prior to 4 (4.7) 5 (5.9) 5 (5.8) first assessment No evidence of disease - 1 (1.2) - Note: Only 4 patients were at risk at the last event time. Median follow-up, mo 9 9 18.4 Summary of TEAEs Regardless of Causality, n (%): Grade ≥3 TEAEs, 36 (41.9); Serious TEAEs, 21 (24.4); TEAEs leading to study drug discontinuation, 8 (9.3); TEAEs leading to death1 5 (5.8)2 {Death3 2 (2.3), Pneumonia 1 (1.2), Cerebral hemorrhage 1 (1.2), Traffic accident 1 (1.2)}. 1Death w ithin 30 days of last dose of zanubrutinib. 2Four events related, 1 event unrelated (traffic accident). 3One subject discontinued treatment due to disease progression prior to death. aThe ef f icacy report was based on modified safety population which excluded patient 20612006 who had local pathological diagnosis of MCL only but did not have confirmation of MCL by central rev iew. 28


 
Updated Data from Zanubrutinib in Combination with Obinutuzumab Remains Consistent in More Patients TN CLL/SLL R/R CLL/SLL R/R FL (n = 20) (n = 25) (n = 36) Follow-up median (range), mo 28.8 (13.9 - 34.8) 28.9 (7.9 – 36.9) 20.1 (2.3-37.2) Best response, n (%) ORR 20 (100.0) 23 (92.0) 26 (72.2) CR* 6 (30.0) 7 (28.0) 14 (38.9) PR 14 (70.0) 16 (64.0) 12 (33.3) SD 0 2 (8.0) 6 (16.7) PD 0 0 4 (11.1) ORR for Del(17p) or p53 6 (100) 8 (80) n/a Safety summary, n (%) for CLL/SLL (n = 45) FL (n=36) : Patients w ith any AE 45 (100.0) 35 (97.2); Patients w ith any treatment related AE 43 (95.6) 30 (83.3); Patients w ith ≥1 grade ≥3 AE 33 (73.3) 19 (52.8); Patients w ith AEs leading to treatment discontinuation 4 (8.9)a 3 (8.3)b. Patients w ith AE leading to death 1 (2.2%), squamous cell carcinoma in patient w ith a history of squamous cell carcinoma. aCLL/SLL: patient with a history of squamous cell carcinoma discontinued due to squamous cell carcinoma, disseminated cryptococcal infection, pneumonia, and neoplasm. bR/R FL: lethargy, ascites, and back pain. *3 out 6 tested in PB were MRD negative at <10-4. FL, f ollicular lymphoma; SD, stable disease. Source: Tam et al, ICML 2019 29


 
Tislelizumab Eric Hedrick, M.D., Chief Advisor


 
Tislelizumab Pivotal Phase 2 in R/R cHL (EHA) Abstract PF469 24th European Hematology Association Congress Eric Hedrick, M.D., Chief Advisor 31


 
Trial Design: Tislelizumab in Phase 2 in R/R cHL Primary endpoint: Tislelizumab - ORR assessed by IRC 200 mg IV Q3W R/R cHL (n=70) Continue treatment until Key Secondary endpoints: PD, unacceptable toxicity, - DOR, PFS, CR rate, TTR or end of study Patients with R/R HL • Failed to achieve a response or progressed after ASCT or received ≥ 2 prior lines of systemic therapy for cHL and was not an ASCT candidate Response assessments: • Responses were assessed by IRC using PET-based imaging according to the Lugano Classification (Cheson 2014) 32


 
Patient and Disease Characteristics Data cut: Nov 26, 2018 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) *Mediastinal mass ratio of 0.33 or size of any single node/nodal mass ≥10 cm in diameter. †All receiv ed ≥ 2 prior regimens. ‡Immunotherapy included brentuximab vedotin, rituximab, cytokine-induced killer cell transfusion, thalidomide, and lenalidomide. 33


 
Best Responses Data cut: Nov 26, 2018 Be st re sponse*, n ( %) n=70 IRC ORR (CR+PR), n (%) [95% CI]† 61 (87.1) [77,93.9] Complete response 44 (62.9) Partial response 17 (24.3) Stable disease 3 (4.3) Progressive disease 5 (7.1) Died before any postbaseline tumor assessment‡ 1 (1.4) *Response Criteria: Lugano 2014 †1-sided Clopper-Pearson 95% CI. ‡Died due to disease progression, not related to study drug. 34


 
Summary of Adverse Events Data cut: Nov 26, 2018 Consistent type and frequency of immune-related AEs TEAE, n (%) n=70 Grade ≥3 TEAE 21 (30) TEAEs in ≥10% of Patients or Grade ≥3 TEAEs Serious TEAE 12* (17.1) in ≥2 Patients Regardless of Causality † TEAE leading to treatment discontinuation 4 (5.7) Pyrexia TEAE leading to death 0 (0.0) Hypothyroidism Immune-related (ir) TEAEs (by aggregate category) Weight increased Upper respiratory tract infection ≥1 irTEAE 27 (38.6) Cough Thyroid disorder 16 (22.9) Pru ritus Pneumonitis 5 (7.1) White blood cell count decreased Skin adverse reactions 6 (8.6) Alanine aminotransferase increased Myositis / rhabdomyolysis / Neutrophil count decreased ‡ 1 (1.4) Gr 1-2 cardiomyopathy Rash Diarrhea Gr ≥3 Nephritis and renal dysfunction 1 (1.4) Anemia Other immune-related reactions (lipase 1(1.4) Pneumonitis increased) 0% 20% 40% 60% Patients (%) *SAEs in all 11 patients determined to be possibly related to tislelizumab. †Pneumonitis (n = 2), f ocal segmental glomerulosclerosis (n = 1), organizing pneumonia (n = 1). ‡Blood creatine phosphokinase increased. TEAE, treatment-emergent adverse events by individual preferred term. 35


 
Progression-Free Survival – 91% of CRs Were Ongoing Data cut: Nov 26, 2018 40 of 44 CR’s and 10 of 17 PRs ongoing Figure out these numbers. 1.0 95.7% + Censored 82.1% 0.8 - Fr ee 0.6 0.4 Progression Survival Probability* 0.2 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Time (months) At Risk 70 70 70 66 63 61 53 48 47 47 28 28 28 28 12 12 12 0 The majority of patients achieved a response by the first response assessment 36


 
Durability of CRs on Tislelizumab Appears Similar to Other PD-1 Antibodies in cHL* Data cut: Nov 26, 2018 Tislelizumab DOR curves by response Nivolumab DOR curves by response BGB-A317-203 CM-205 study *Data from separate trials. Limitations regarding cross-trial comparisons apply. *Response criteria in tislelizumab study: Lugano 2014 **Response criteria in nivolumab study: Cheson 2007, confirmation of radiographic CR by PET. Sources: BeiGene data on f ile; J Clin Oncol 36:1428-1439. 37


 
Tislelizumab in NPC (ASCO) Abstract 2556 American Society of Clinical Oncology Eric Hedrick, M.D., Chief Advisor 38


 
Tislelizumab Nasopharyngeal Carcinoma Cohort from Global Phase 1 NPC (n=21) Preliminary Antitumor Activity Median age, years (min, max) 48 (35, 61) Male 17 (81) • A total of 21 patients were evaluable for antitumor Sex Female 4 (19) activity, defined as any patient who had measurable Prior anticancer radiotherapy 21 (100) disease at baseline and at least one postbaseline tumor assessment 0 1 (5) 1 6 (29) Prior anticancer therapy regimens • A total of nine patients (n=8, PD-L1+; n=1, PD-L1-) 2 4 (19) achieved a confirmed PR, nine patients (n=6, PD-L1+; ≥3 10 (48) n=2, PD-L1-; n=1, unknown) achieved confirmed SD 0 8 (38) ECOG status 1 13 (62) • Confirmed ORR was 43% (95% confidence interval Poorly differentiated 2 (10) [CI]: 21.8-66.0) Histologic grade Undifferentiated 16 (76) • CBR and DCR were 62% (95% CI: 38.4-81.9) Unknow n 3 (14) and 86% (95% CI: 63.7-97.0), respectively Locally advanced 3 (14) Tumor stage • Median duration of response was 8.3 months (95% CI: Metastatic 18 (86) 3.9, not reached); follow-up time for responders was PD-L1 positive (PD-L1+)* 16 (76) 4.8 months (95% CI: 2.1-11.1) PD-L1 status PD-L1 negative (PD-L1-)* 4 (19) Unknow n 1 (5) Data presented as n (%) except for age. *PD-L1-positive status defined as ≥10% of tumor cells with PD-L1 membrane staining, as retrospectively assessed by central lab; †PD-L1-negative status defined as <10% of tumor cells with PD- L1 membrane staining, as retrospectively assessed by central lab. NPC, nasopharyngeal carcinoma; PD-L1, programmed cell death ligand-1. 39


 
Key Takeaways Eric Hedrick, M.D., Chief Advisor 40


 
Zanubrutinib Key Takeaways • Results from non-randomized MYD88WT cohort of Phase 3 trial in WM confirmed activity of zanubrutinib in this difficult- to-treat population, with ORR and VGPR rates consistent with results from MYD88WT patients treated in Phase 1 • First presentation of pivotal Phase 2 data in Chinese patients with relapsed or refractory CLL demonstrated efficacy consistent with the experience with zanubrutinib in Western CLL patients • Updated integrated safety analysis of data from 682 patients with a median exposure of 13.4 months continues to show low rates of atrial fibrillation, serious bleeding, and diarrhea • Updated pivotal China R/R MCL data demonstrated high CR rate • Zanubrutinib / GAZYVA combination appears highly active in FL and supports ongoing pivotal Phase 2 trial 41


 
Tislelizumab Key Takeaways • Follow-up from the Phase 2 study of tislelizumab in Chinese patients with classical Hodgkin’s lymphoma confirms a high complete response rate and encouraging durability of complete responses • ASCO data show encouraging activity of tislelizumab in nasopharyngeal cancer and supports ongoing Phase 3 • Tislelizumab is under CDE review for approval in cHL and urothelial cancer in China, and the broad Phase 3 program is maturing, with initial read-out in HCC and completion of enrollment to multiple trials in 2019 42


 
Q&A 43


 
Thank You 44


 
Backup 45


 
PD-1 Inhibitor Data in R/R cHL* Pembrolizumab and Nivolumab Pembrolizumab1 Nivolumab2 Company Mer c k BMS n 210 243 A SCT-ineligible OR A SCT-failure Eligibility A SCT-failure Prior brentuximab vedotina Prior brentuximab vedotina Prior Lines, med (range) 4 (1-12) 4 (2-15) Prior therapy A SCT 129 (61%) 243 (100%) Brentuximab Vedotin 150 (71%) 180 (74%) Follow -up (med) 15.9 months 18 months Response Criteria Cheson 2007 Lugano 2014 Cheson 2007 ORR 71% 73% 69% CR 25% 31% 16% PR 47% 42% 53% SD 12% 8% 19% * Data from separate trials. Limitations regarding cross-trial comparisons apply. Sources: 1 Blood 2017 130:4085; 2 JCO 2018 a Prior brentuximab vedotin required for 2 of 3 study cohorts 46


 
Reported PD-1 Inhibitor Data in R/R cHL* Sintilimaband Camrelizumab Sintilimab1 Camrelizumab2 Company Innovent Hengrui n 96 66 Eligibility > 2 prior lines of therapya > 2 prior lines of therapya Prior Lines, med (range) 3 (1-13) 3 (2-10) Prior therapy A SCT 18 (19%) 9 (14%) Brentuximab Vedotin NR 5 (8%) Follow -up (med) 14 >6 Response Criteria Cheson 2007 Lugano 2014 ORR 85% 85% CR 29% 30% PR 56% 54% SD 13% 12% * Data from separate trials. Limitations regarding cross-trial comparisons apply. Sources: 1 ASCO 2019 (Abstract 7533); 2 CSCO 2018 a ineligibility for ASCT was not required 47


 
Reported PD-1 Inhibitor Data in R/R cHL Tislelizumab Tislelizumab1 Company BeiGene n 70 A SCT-ineligible Eligibility A SCT-failure Prior Lines, med (range) 3 (2-11) Prior therapy A SCT 13 (19%) Brentuximab Vedotin 4 (5.7%) Follow -up (med) 13 mo Response Criteria Lugano 2014 ORR 87% CR 63% PR 24% SD 4% Sources: 1 Song Et al., EHA 2019 a ineligibility for ASCT was not required 48


 
Exhibit
Exhibit 99.2

BeiGene and SpringWorks Therapeutics Announce the Formation of MapKure to Develop BGB-3245, an Investigational, Selective Next-Generation RAF Kinase Inhibitor
CAMBRIDGE, Mass., BEIJING, China and STAMFORD, Conn. – June 18, 2019 – BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, and SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, today announced the formation of MapKure, LLC, a newly created entity that is jointly owned by BeiGene and SpringWorks. MapKure intends to develop BGB-3245, an investigational, oral, selective small molecule inhibitor of monomer and dimer forms of activating B-RAF mutations including V600 BRAF mutations, non-V600 B-RAF mutations, and RAF fusions. These mutations and fusions have been identified in a number of solid tumors to be drivers of cancer growth, including in non-small cell lung cancer, colorectal cancer, thyroid cancer, and brain tumors.
BGB-3245 was discovered by BeiGene scientists and is currently in preclinical development. Under the terms of the agreements, SpringWorks has made an equity investment into MapKure and BeiGene has contributed an exclusive royalty and milestone-bearing license to develop and commercialize BGB-3245 outside of Asia, but including rights to Japan, in exchange for a majority ownership position in MapKure. MapKure will form a joint steering committee that will oversee clinical development and operations for BGB-3245, as well as a Board of Directors. Both the joint steering committee and the Board will include members from BeiGene, SpringWorks and MapKure’s CEO. Further terms of the agreements were not disclosed.
Neal Rosen, M.D., Ph.D., Director of the Center for Mechanism-Based Therapeutics and the incumbent of the Enid A. Haupt Chair in Medical Oncology at Memorial Sloan-Kettering Cancer Center, is the founding member of the MapKure Scientific Advisory Board.
“Preclinical data demonstrate that BGB-3245 could potentially address a significant unmet medical need for patients with non-V600 B-RAF mutations or RAF fusions that are presently unaddressed with approved B-RAF-directed therapies. In addition, BGB-3245’s preclinical activity in cancer models driven by V600 B-RAF mutations demonstrate that it could provide an additional therapeutic option for these patients with the potential to reduce dimer-driven resistances,” said Dr. Rosen. “I look forward to being part of this endeavor to evaluate the therapeutic potential of BGB-3245.”





BeiGene and SpringWorks plan for MapKure to initiate an adaptive Phase 1 dose-escalation and expansion study of BGB-3245 in solid tumor patients harboring specific B-RAF driver mutations and RAF fusions, as well as in patients who have developed resistance to first-generation BRAF inhibitors. MapKure intends to enter into service agreements with both BeiGene and SpringWorks to enable the execution of this study and to perform other activities to support MapKure operations. Subsequent clinical development efforts with BGB-3245 may also include rational combination therapies, including with MEK inhibitors such as PD-0325901, which is being developed by SpringWorks.
This effort, once again, shows our commitment to developing innovative medicines for cancer patients with few or no treatment options. We are pleased to expand our collaboration with SpringWorks to take this potentially first-in-class product candidate into human trials,” said John V. Oyler, Co-Founder, Chief Executive Officer and Chairman of BeiGene.
“SpringWorks is committed to identifying and advancing medicines for underserved patient populations. We are delighted to be working again with BeiGene, as well as with several leaders in the targeted oncology field who have been invited to join the MapKure Scientific Advisory Board,” said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics and member of the MapKure Board of Directors.
Lusong Luo, Ph.D., Senior Vice President of External Innovation at BeiGene, will be Acting CEO of MapKure and a member of the MapKure Board of Directors.
“BGB-3245 has demonstrated antitumor activity in a variety of preclinical cancer models, including those driven by mutations for which there are currently no approved therapies,” said Dr. Luo. “I look forward to advancing BGB-3245 into human trials in hopes of providing a treatment for these patients.”
In September 2018, BeiGene and SpringWorks announced a global clinical collaboration agreement to evaluate the safety, tolerability, and preliminary efficacy of combining BeiGene's investigational RAF dimer inhibitor, lifirafenib (BGB-283) and SpringWorks' investigational MEK inhibitor, PD-0325901, in patients with advanced solid tumors. Under the collaboration, BeiGene recently began a Phase 1b clinical trial to evaluate this combination in patients with advanced or refractory solid tumors that harbor RAS mutations, RAF mutations, and other MAPK pathway aberrations.



2




About MapKure
MapKure is a research-stage company that was created in 2019 to develop precision medicines to help patients with life-threatening diseases, with an initial focus on cancer. By focusing on genetically defined disease drivers, MapKure is positioned to provide transformative medicines to patients whose unmet medical needs are largely unaddressed. Jointly owned by BeiGene, Ltd. and SpringWorks Therapeutics, Inc., MapKure is currently developing BGB-3245, a preclinical oral, small molecule inhibitor of specific BRAF mutations, including B-RAF non-V600 mutations and RAF fusions, which have been identified in numerous solid tumor indications to be drivers of tumor growth. In addition to its intended use as a monotherapy in several genetically defined solid tumor types, BGB-3245 also has the potential to be used in rational combination therapies in the future.
About BeiGene
BeiGene is a global, commercial-stage, research-based biotechnology company focused on molecularly-targeted and immuno-oncology cancer therapeutics. With a team of approximately 2,400 employees in China, the United States, Australia and Europe, BeiGene is advancing a pipeline consisting of novel oral small molecules and monoclonal antibodies for cancer. BeiGene is also working to create combination solutions aimed to have both a meaningful and lasting impact on cancer patients. BeiGene markets ABRAXANE® (nanoparticle albumin–bound paclitaxel), REVLIMID® (lenalidomide), and VIDAZA® (azacitidine) in China under a license from Celgene Corporation. For more information, please visit www.beigene.com.
About SpringWorks Therapeutics
At SpringWorks Therapeutics, a clinical-stage biopharmaceutical company, we are driven to develop life-changing medicines for patients with severe rare diseases and cancer. Since our launch in 2017, we have worked to identify and advance promising science, beginning with our licensed clinical therapies from Pfizer Inc. We pioneer efficient pathways for drug development, leveraging shared-value partnerships with patient advocacy groups, innovators in industry and academia, and investors so that together, we can unlock the potential of science and bring new therapies to underserved patients. Nirogacestat, our gamma secretase inhibitor for the treatment of desmoid tumors is currently in a Phase 3 clinical trial, and SpringWorks Therapeutics expects to initiate a Phase 2b study of PD-0325901, our MEK 1/2 inhibitor for neurofibromatosis type 1 patients with plexiform neurofibromas, in the third quarter of 2019. PD-0325901 also holds promise as the backbone for combination therapies to treat metastatic solid

3




tumors. At SpringWorks, we ignite the power of promising science to unleash new possibilities for patients. For more information, please visit www.springworkstx.com.
Follow SpringWorks Therapeutics on social media: @SpringWorksTx and LinkedIn.
BeiGene Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the encouraging pre-clinical data and therapeutic potential of BGB-3245 and plans for the operations of MapKure and clinical development of BGB-3245. 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, 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 press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.
BeiGene Investor Contact
 
BeiGene Media Contact
 
Craig West
 
Liza Heapes
 
+1 857-302-5189
 
+1 857-302-5663
 
ir@beigene.com
 
media@beigene.com
 
SpringWorks Contact:
 
 
Kim Diamond
 
 
Vice President, Communications and Investor Relations
 
 
Phone: 646-661-1255
 
 
Email: kdiamond@springworkstx.com
 
 

4

Exhibit
Exhibit 99.3

BeiGene Announces Updated Results from Two Ongoing Clinical Trials of Zanubrutinib in Patients with Mantle Cell Lymphoma in Presentations at the 15th International Conference on Malignant Lymphoma (ICML)
Company to Host Investor Conference Call and Webcast of Mid-2019 Clinical Data Updates on Thursday, June 20 at 8:00 a.m. EDT
CAMBRIDGE, Mass. and BEIJING, China, June 19, 2019 (GLOBE NEWSWIRE) -- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced results from two ongoing clinical studies of its investigational BTK inhibitor zanubrutinib in patients with mantle cell lymphoma (MCL) in two presentations at the 15th International Conference on Malignant Lymphoma (ICML), taking place June 18-22, 2019 in Lugano, Switzerland.
“With longer follow-up, we continue to be encouraged by the clinical results of zanubrutinib in patients with MCL. The deep, durable responses shown in these two presentations at ICML provide additional support for our new drug application in MCL in China, which is currently under priority review,” said Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene. “We hope that zanubrutinib will become an impactful treatment for patients with MCL and other B-cell malignancies.”
Summary of Updated Clinical Results from the Pivotal Phase 2 Trial Being Conducted in China
This single-arm, open-label, multi-center, pivotal Phase 2 trial of zanubrutinib as a monotherapy in patients with relapsed/refractory (R/R) MCL (clinicaltrials.gov identifier: NCT03206970) is being conducted in China, and enrolled 86 patients who had received a median of two (1-4) prior lines of therapy. Patients were treated with zanubrutinib, dosed at 160 mg orally twice-daily (BID). The primary endpoint of the trial was overall response rate (ORR) assessed by independent review committee (IRC) using PET-based imaging according to the Lugano Classification 2014.
As of the February 15, 2019 data cutoff, 52 patients (60.5%) remained on study treatment. The median follow-up time for patients enrolled in the trial was 18.4 months (0.3-23.5). Results included:
The investigator-assessed (INV) ORR was 83.7% (72/86); the complete response (CR) rate was 77.9% (67/86) and the partial response (PR) rate was 5.8% (5/86). At an earlier data cutoff of March 2018 (8.2 months follow-up), the

1



ORR, CR and PR were 84.7%, 72.9%, and 11.8% per investigator assessment, and 83.5%, 58.8%, and 24.7% per IRC assessment, respectively;
The 15-month progression-free survival (PFS) by investigator was estimated at 72.1%; median PFS follow-up was 19.1 months (0.0-22.3);
With 16.4 months median follow-up (2.3-19.5), the duration of response (DOR) by investigator at 15 months was 67.4%;
Zanubrutinib tolerability was generally consistent with previous reports of zanubrutinib treatment in patients with various B-cell malignancies. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with the most frequently reported being neutrophil count decreased (44.2%), upper respiratory tract infection (34.9%), rash (33.7%), white blood cell count decrease (31.4%), and platelet count decrease (25.6%);
Grade 3 TEAEs were reported in 36 patients (41.9%), with the most frequently reported being neutrophil count decrease (18.6%), lung infection (7.0%), white blood cell count decrease (5.8%), and anemia (5.8%);
Five patients (5.8%) had TEAEs leading to death (one case each of pneumonia, cerebral hemorrhage, traffic accident, and two cases of death with unknown cause); and
Among TEAEs of special interest for BTK inhibitors, hypertension was reported in 13 patients (15.1%), petechiae/purpura/contusion in four patients (4.7%), and major hemorrhage in three patients (3.5%); no cases of atrial fibrillation/flutter, secondary primary malignancy, or tumor lysis syndrome were reported in this trial.
“Zanubrutinib demonstrated high activity in patients with R/R MCL, with 84% of patients achieving objective response and now an investigator-assessed complete response rate observed at 78%. The responses achieved have been generally well-tolerated as well,” said Yuqin Song, M.D., Ph.D., Associate Professor of Medical Oncology, Deputy Director of the Lymphoma Department at Peking University Cancer Hospital in China, and the presenting author of the pivotal Phase 2 trial in Chinese patients.
Summary of Updated Clinical Results from the Global Phase 1/2 Trial
This open-label, multi-center Phase 1/2 trial of zanubrutinib as a monotherapy (clinicaltrials.gov identifier: NCT02343120) in patients with different subtypes of B-cell malignancies, including MCL, is being conducted in the United States, Australia, Italy, South Korea, New Zealand, and the United Kingdom.

2



As of the December 13, 2018 data cut-off, 53 patients with treatment naïve (TN, n=16) or R/R (n=37) MCL have been enrolled in the trial and the median follow-up time was 15.4 months (0.1-38.2). Forty-eight patients (all 37 R/R and 11 TN) were evaluable for efficacy with median follow-up time of 16.7 months (1.6-38.2) in this analysis, per the Lugano 2014 Classification. At the time of the data cutoff, 27 patients (13 TN and 14 R/R) remained on study treatment. Updated results included:
The investigator-assessed ORR was 85.4% (41/48); the CR rate was 29.2% (14/48) and the PR rate was 56.3% (27/48). The majority of patients were assessed via CT-scan; PET scan was optional per trial protocol;
The median DOR was 16.2 months (0.03-28.2) for all patients. The median PFS for patients with R/R MCL was 17.3 months;
The majority of adverse events (AEs) were grade 1 or 2 in severity. The most frequently reported AEs included contusion (39.6%), diarrhea (34.0%), upper respiratory tract infection (26.4%), constipation (22.6%), fatigue (22.6%), and rash (18.9%);
Grade 3 AEs were reported in 54.7% patients, with the most frequent being anemia (9.4%), myalgia (5.7%), cellulitis (5.7%), pleural effusion (5.7%), and pneumonia (5.7%);
Discontinuation due to AEs occurred in 18.9% patients with two determined to be related to study drug (one case each of peripheral edema and subdural hematoma); and
There were five deaths due to AEs, which were all determined by the investigators to be unrelated to zanubrutinib treatment.
“The updated results from this Phase 1/2 global trial suggested that zanubrutinib was generally well-tolerated and highly active in patients with MCL. These data support further evaluation of zanubrutinib in late-stage clinical studies,” commented Constantine Tam, M.D., Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at the Peter MacCallum Cancer Center and Director of Hematology at St. Vincent’s Hospital, Australia, and lead author of the poster presentation of results from the global Phase 1/2 trial.




3



Mid-2019 Clinical Data Update Conference Call and Webcast Information:
BeiGene will host a conference call and webcast on Thursday, June 20 at 8:00 a.m. EDT. Investors and analysts are invited to join the conference call using the following dial-in information:
U.S. Toll-Free: +1 (844) 461-9930
U.S. Toll: +1 (478) 219-0535
Hong Kong Toll-Free: +852 800 279 19250
China Toll-Free: +86 800 914 686
Conference ID: 1790069
A live webcast of the conference call can be accessed from the investors section of BeiGene’s website at http://ir.beigene.com/ or http://hkexir.beigene.com. An archived replay will be available two hours after the event for 90 days.
About Mantle Cell Lymphoma
Lymphoma is a diverse group of malignancies that originates from B-, T- or NK- cells. Mantle cell lymphoma (MCL) is typically an aggressive form of non-Hodgkin lymphoma (NHL) that arises from B-cells originating in the “mantle zone.” In 2015, about 88,200 new cases and 52,100 cancer deaths of lymphoma were expected in Mainland China, making it the 12th most common cancer and the 11th leading cause of cancer death. In the United States, about 70,800 new cases of NHL were expected in 2014, with MCL representing about six percent (about 4,200 cases) of all new cases of NHL in the United States. Mantle cell lymphoma usually has a poor prognosis, with a median survival of three to four years, although occasionally patients may have an indolent course. Frequently, mantle cell lymphoma is diagnosed at a later stage of disease.
About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated in a broad pivotal clinical program globally as a monotherapy and in combination with other therapies to treat various B-cell malignancies.
Clinical trials of zanubrutinib include a fully-enrolled, global Phase 3 clinical trial in patients with Waldenström macroglobulinemia (WM) comparing zanubrutinib to ibrutinib, currently the only approved BTK inhibitor for WM; a global Phase 3 clinical trial in patients with previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); a pivotal Phase 2 trial in patients with relapsed/refractory (R/R) follicular lymphoma in combination with GAZYVA® (obinutuzumab); a Phase 3 trial comparing zanubrutinib to ibrutinib in patients with R/R CLL/SLL; and a global Phase 1

4



trial. In China, BeiGene has completed two pivotal Phase 2 clinical trials of zanubrutinib in patients with R/R MCL and R/R CLL/SLL and the enrollment in the pivotal Phase 2 clinical trials in patients with WM.
Zanubrutinib has been granted by the U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of patients with WM, and Breakthrough Therapy designation for the treatment of adult patients with MCL who have received at least one prior therapy. The New Drug Applications (NDAs) in China for R/R MCL and R/R CLL/SLL have been accepted by the China National Medical Products Administration (NMPA) and granted priority review. BeiGene plans to submit its first NDA in the U.S. for zanubrutinib in 2019 or early 2020.
About BeiGene
BeiGene is a global, commercial-stage, research-based biotechnology company focused on molecularly-targeted and immuno-oncology cancer therapeutics. With a team of over 2,500 employees in China, the United States, Australia and Europe, BeiGene is advancing a pipeline consisting of novel oral small molecules and monoclonal antibodies for cancer. BeiGene is also working to create combination solutions aimed to have both a meaningful and lasting impact on cancer patients. BeiGene markets ABRAXANE® (nanoparticle albumin–bound paclitaxel), REVLIMID® (lenalidomide), and VIDAZA® (azacitidine) in China under a license from Celgene Corporation.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the encouraging clinical data from clinical trials of zanubrutinib and BeiGene’s advancement of, and anticipated clinical development, regulatory milestones and commercialization of zanubrutinib. 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

5



additional funding for operations and to complete the development and commercialization of its drug candidates, 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 press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.
BeiGene Investor Contact
 
BeiGene Media Contact
 
Craig West
 
Liza Heapes
 
+1 857-302-5189
 
+1 857-302-5663
 
ir@beigene.com
 
media@beigene.com
 



6

Exhibit
Exhibit 99.4
          


BeiGene Presents Pivotal Phase 2 Clinical Results of Zanubrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma at the 15th International Conference on Malignant Lymphoma (ICML)
Company to Host Investor Conference Call and Webcast of Mid-2019 Clinical Data Updates Today, Thursday, June 20 at 8:00 a.m. EDT
CAMBRIDGE, Mass. and BEIJING, China, June 20, 2019 (GLOBE NEWSWIRE) -- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced results from an ongoing pivotal Phase 2 clinical study of its investigational BTK inhibitor zanubrutinib being conducted in China in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in an oral presentation at the 15th International Conference on Malignant Lymphoma (ICML), taking place June 18-22, 2019 in Lugano, Switzerland.
“The results of this trial in patients with relapsed/refractory CLL or SLL are part of our NDA in China, where patients with this disease have far fewer treatment options than in the West. At BeiGene, we are committed to improving treatment outcomes and access for patients worldwide,” said Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene.
Summary of Updated Clinical Results from the Pivotal Phase 2 Study Being Conducted in China
This single-arm, pivotal Phase 2 trial (clinicaltrials.gov identifier: NCT03206918) of zanubrutinib as a monotherapy in patients with R/R CLL/SLL is the basis for BeiGene’s new drug application (NDA) for this indication which is currently under review by the China National Medical Products Administration (NMPA). The trial is being conducted in China, and enrolled 91 patients from 11 study centers, including 82 patients with CLL and nine with SLL. Patients were treated with zanubrutinib, dosed at 160 mg orally twice-daily (BID). The primary endpoint of the trial was overall response rate (ORR) assessed by independent review committee (IRC) using iwCLL 2008 criteria for CLL and CT-based assessment according to the Lugano Classification 2014 for SLL.
As of the December 14, 2018 data cutoff, 75 patients (82.4%) remained on study treatment. The median follow-up time for patients enrolled in the trial was 15.1 months (0.8-21.2). Results included:

1




The ORR by IRC was 84.6% (77/91); the complete response (CR) rate was 3.3% (3/91); the partial response (PR) rate was 59.3% (54/91) and the PR with lymphocytosis (PR-L) was 22.0% (20/91). ORRs per IRC were generally consistent across different subgroups;
The 12-month progression-free survival (PFS) was estimated at 87.2% and the median PFS had not been reached with median PFS follow-up at 12.9 months (0.8-20.4);
Zanubrutinib tolerability was generally consistent with previous reports of zanubrutinib treatment in patients with various B-cell malignancies. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with the most frequently reported TEAEs being neutrophil count decrease (68.1%), upper respiratory tract infection (45.1%), purpura (34.1%), and platelet count decreased (33.0%);
Grade 3 TEAEs were reported in 75.8% of patients, with the most frequently reported being neutrophil count decrease (44.0%), lung infection (9.9%), upper respiratory tract infection (9.9%), platelet count decrease (8.8%), and anemia (8.8%); and
Three patients had TEAEs leading to death (one case each of lung infection/cardiac failure/respiratory, cardiopulmonary failure, and multiple organ dysfunction syndrome in the setting of disease progression); these were determined unlikely or unrelated to zanubrutinib treatment.
“With trial enrollment completed in 2017, we are continuing to follow its participants to assess zanubrutinib’s activity for patients with R/R CLL or SLL. We are pleased that these data demonstrated 85% ORR by IRC and that the tolerability has been consistent with previous reports,” said Wei Xu, M.D., Ph.D., Deputy director of the hematology department at The First Affiliated Hospital of Nanjing Medical University in China, and the presenting author of the trial.





2



Today’s Mid-2019 Clinical Data Update Conference Call and Webcast Information:
BeiGene will host a conference call and webcast today, Thursday, June 20 at 8:00 a.m. EDT. Investors and analysts are invited to join the conference call using the following dial-in information:
U.S. Toll-Free: +1 (844) 461-9930
U.S. Toll: +1 (478) 219-0535
Hong Kong Toll-Free: +852 800 279 19250
China Toll-Free: +86 800 914 686
Conference ID: 1790069
A live webcast of the conference call can be accessed from the investors section of BeiGene’s website at http://ir.beigene.com/ or http://hkexir.beigene.com. An archived replay will be available two hours after the event for 90 days.
About Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of non-Hodgkin lymphoma, a type of blood cancer, that arise from B lymphocytes. CLL and SLL are essentially the same disease, with the only difference being the location where the cancer primarily occurs. When most of the cancer cells are located in the peripheral blood and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL.
About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated in a broad pivotal clinical program globally as a monotherapy and in combination with other therapies to treat various B-cell malignancies.
Clinical trials of zanubrutinib include a fully-enrolled, global Phase 3 clinical trial in patients with Waldenström macroglobulinemia (WM) comparing zanubrutinib to ibrutinib, currently the only approved BTK inhibitor for WM; a global Phase 3 clinical trial in patients with previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); a pivotal Phase 2 trial in patients with relapsed/refractory (R/R) follicular lymphoma in combination with GAZYVA® (obinutuzumab); a Phase 3 trial comparing zanubrutinib to ibrutinib in patients with R/R CLL/SLL; and a global Phase 1 trial. In China, BeiGene has completed two pivotal Phase 2 clinical trials of zanubrutinib

3



in patients with R/R MCL and R/R CLL/SLL and the enrollment in the pivotal Phase 2 clinical trials in patients with WM.
Zanubrutinib has been granted by the U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of patients with WM, and Breakthrough Therapy designation for the treatment of adult patients with MCL who have received at least one prior therapy. The New Drug Applications (NDAs) in China for R/R MCL and R/R CLL/SLL have been accepted by the China National Medical Products Administration (NMPA) and granted priority review. BeiGene plans to submit its first NDA in the U.S. for zanubrutinib in 2019 or early 2020.
About BeiGene
BeiGene is a global, commercial-stage, research-based biotechnology company focused on molecularly-targeted and immuno-oncology cancer therapeutics. With a team of over 2,500 employees in China, the United States, Australia and Europe, BeiGene is advancing a pipeline consisting of novel oral small molecules and monoclonal antibodies for cancer. BeiGene is also working to create combination solutions aimed to have both a meaningful and lasting impact on cancer patients. BeiGene markets ABRAXANE® (nanoparticle albumin–bound paclitaxel), REVLIMID® (lenalidomide), and VIDAZA® (azacitidine) in China under a license from Celgene Corporation.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the encouraging clinical data from clinical trials of zanubrutinib and BeiGene’s advancement of, and anticipated clinical development, regulatory milestones and commercialization of zanubrutinib. 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

4



complete the development and commercialization of its drug candidates, 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 press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.

BeiGene Investor Contact
 
BeiGene Media Contact
 
Craig West
 
Liza Heapes
 
+1 857-302-5189
 
+1 857-302-5663
 
ir@beigene.com
 
media@beigene.com
 


5

Exhibit
Exhibit 99.5
           


BeiGene Announces Phase 1b Clinical Results of Zanubrutinib in Combination with GAZYVA® (Obinutuzumab) in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Follicular Lymphoma at the 15th International Conference on Malignant Lymphoma (ICML)
CAMBRIDGE, Mass. and BEIJING, China, June 20, 2019 (GLOBE NEWSWIRE) -- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced results from an ongoing Phase 1b clinical study of its investigational BTK inhibitor zanubrutinib in combination with GAZYVA® (obinutuzumab) in patients with relapsed/refractory (R/R) or treatment naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and patients with R/R follicular lymphoma (FL). These data were included in an oral presentation at the 15th International Conference on Malignant Lymphoma (ICML), taking place June 18-22, 2019 in Lugano, Switzerland.
“These updated data provide further evidence for the rational combination of zanubrutinib and obinutuzumab, and build upon the foundation supporting our global pivotal Phase 2 trial comparing obinutuzumab plus zanubrutinib to obinutuzumab alone as a treatment for patients with R/R follicular lymphoma. It is our hope that we will continue to see deep and durable responses for these patients,” said Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene.
“These data demonstrated that zanubrutinib, in combination with the anti-CD20 monoclonal antibody obinutuzumab was generally well-tolerated, with the majority of adverse events being grade 1 or 2. In addition, the early finding of peripheral blood MRD negativity in three out of six patients with CLL/SLL merits further investigation,” commented Constantine S. Tam, M.D., Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at the Peter MacCallum Cancer Center and Director of Hematology at St. Vincent’s Hospital, Australia, and presenting author of the trial.
Summary of Updated Clinical Results from the Phase 1b Combination Trial with Obinutuzumab in Patients with TN or R/R CLL/SLL and R/R FL
The open-label, Phase 1b trial (clinicaltrials.gov identifier: NCT02569476) of zanubrutinib in combination with obinutuzumab in patients with B-cell malignancies is being conducted in Australia, the United States, and South Korea, and consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, including patients with TN or R/R CLL/SLL and patients with R/R FL. The dose-escalation component tested zanubrutinib at 320 mg once a day (QD) or 160 mg twice

1



daily (BID) in 28-day cycles, in combination with obinutuzumab; obinutuzumab was administered in line with standard CLL dosing (three loading doses of 1000 mg weekly followed by 1000 mg on day one of cycles 2–6). Patients enrolled in the Phase 1b dose-expansion received zanubrutinib at 160 mg twice daily (BID) in 28-day cycles, in combination with obinutuzumab, which was administered with standard CLL dosing (three loading doses of 1000 mg weekly followed by 1000 mg on the first day of cycles 2–6). As of the February 28, 2019 data cutoff, a total of 81 patients with CLL/SLL or FL were enrolled in the trial, including 45 patients with CLL/SLL and 36 patients with FL. The primary endpoint of the expansion trial was investigator-assessed overall response rate (ORR) and duration of response (DOR) by standard 2007 International Working Group criteria.
As of the data cutoff, 51 patients (62.9%) remained on study treatment, including 33 patients (73.3%) with CLL/SLL and 18 patients (50%) with FL. The median follow-up time for patients with CLL/SLL was 28.9 months (7.9-36.9) and 20.1 months (2.3-37.2) for patients with FL. Results included:
Of the 20 patients with TN CLL/SLL, the ORR was 100%; the complete response (CR) rate was 30.0% (6/20); and the partial response (PR) rate was 70.0% (14/20). Median follow-up for these patients was 28.8 months (13.9-34.8);
Of the 25 patients with R/R CLL/SLL, the ORR was 92.0% (23/25); the CR was 28.0% (7/25); and the PR was 64.0% (16/25). Median follow-up for these patients was 28.9 months (7.9-36.9);
Of the six patients with CLL/SLL who achieved CR and were tested, three were observed to be MRD negative in the peripheral blood;
Of the 36 patients with R/R FL, the ORR was 72.2% (26/36); the CR was 38.9% (14/36); and the PR was 33.3% (12/36). Median response follow-up was 20.1 months (2.3-37.2);
For patients with TN or R/R CLL/SLL the median progression free survival (PFS) had not been reached, with 73.3% of patients remaining on treatment. For patients with R/R FL, the median PFS was 24.9 months (0.7-36.4), with 50% of patients remaining on treatment;
The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity;
The most common TEAEs in patients with CLL/SLL were upper respiratory tract infection (URTI, 51.2%), neutropenia (44.4%), contusion (33.3%), fatigue

2



(26.7%), and diarrhea (26.7%). The most common adverse events (AEs) in patients with FL were URTI (38.9%), contusion (27.8%), fatigue (25.0%), cough (22.2%), and thrombocytopenia (19.5%);
The most common grade ≥3 AEs in patients with CLL/SLL were neutropenia (31.1%), pneumonia (8.9%), and thrombocytopenia (6.7%). The most common grade ≥3 AEs in patients with FL were neutropenia (13.9%), thrombocytopenia (5.6%), and back pain (2.8%); and
One patient with CLL/SLL had a TEAE leading to death (metastatic squamous cell carcinoma).
About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated in a broad pivotal clinical program globally as a monotherapy and in combination with other therapies to treat various B-cell malignancies.
Clinical trials of zanubrutinib include a fully-enrolled, global Phase 3 clinical trial in patients with Waldenström macroglobulinemia (WM) comparing zanubrutinib to ibrutinib, currently the only approved BTK inhibitor for WM; a global Phase 3 clinical trial in patients with previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); a pivotal Phase 2 trial in patients with relapsed/refractory (R/R) follicular lymphoma in combination with GAZYVA® (obinutuzumab); a Phase 3 trial comparing zanubrutinib to ibrutinib in patients with R/R CLL/SLL; and a global Phase 1 trial. In China, BeiGene has completed two pivotal Phase 2 clinical trials of zanubrutinib in patients with R/R MCL and R/R CLL/SLL and the enrollment in the pivotal Phase 2 clinical trials in patients with WM.
Zanubrutinib has been granted by the U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of patients with WM, and Breakthrough Therapy designation for the treatment of adult patients with MCL who have received at least one prior therapy. The New Drug Applications (NDAs) in China for R/R MCL and R/R CLL/SLL have been accepted by the China National Medical Products Administration (NMPA) and granted priority review. BeiGene plans to submit its first NDA in the U.S. for zanubrutinib in 2019 or early 2020.




3



About BeiGene
BeiGene is a global, commercial-stage, research-based biotechnology company focused on molecularly-targeted and immuno-oncology cancer therapeutics. With a team of over 2,500 employees in China, the United States, Australia and Europe, BeiGene is advancing a pipeline consisting of novel oral small molecules and monoclonal antibodies for cancer. BeiGene is also working to create combination solutions aimed to have both a meaningful and lasting impact on cancer patients. BeiGene markets ABRAXANE® (nanoparticle albumin–bound paclitaxel), REVLIMID® (lenalidomide), and VIDAZA® (azacitidine) in China under a license from Celgene Corporation.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the encouraging clinical data from clinical trials of zanubrutinib, and BeiGene’s advancement of, and anticipated clinical development, regulatory milestones and commercialization of zanubrutinib. 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, 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 press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.


4



BeiGene Investor Contact
 
BeiGene Media Contact
 
Craig West
 
Liza Heapes
 
+1 857-302-5189
 
+1 857-302-5663
 
ir@beigene.com
 
media@beigene.com
 


5