Beone Medicines Ltd. Class A · SSE:688235
Beone Medicines Ltd. Class A — BeiGene — Technical Presentation (December 2019)
47 slides from Beone Medicines Ltd. Class A's technical presentation, Dec 16, 2019
Slide 1: ASPEN Results Conference Call
Exhibit 99.1 ASPEN Results Conference Call December 16, 2019
Slide 2: Howard Liang, CFO and Chief Strategy Officer
Howard Liang, Ph.D. CFO and Chief Strategy Officer 2
Slide 3: Agenda
Agenda Welcome – Howard Liang Introduction – John Oyler ASPEN Results – Jane Huang BRUKINSA Development – Eric Hedrick BRUKINSA Commercialization – Josh Neiman Concluding Remarks – John Oyler Q&A 3
Slide 4: Forward-looking statements 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 clini
Slide 5: John V. Oyler, Chairman, Co-founder & CEO
John V. Oyler Chairman, Co-founder & CEO 5
Slide 6: Jane Huang, Chief Medical Officer, Hematology
Jane Huang, M.D. Chief Medical Officer, Hematology 6
Slide 7: Executive Summary
Executive Summary • ASPEN is the first randomized Phase 3 study comparing two BTK inhibitors in any indication & the largest prospective randomized Phase 3 study in Waldenström’s Macroglobulinemia (WM) • The difference in the primary endpoint of the study (VGPR+CR rate: 28.9% zanubrutinib vs 19.8% i
Slide 8: ASPEN: Phase 3 Study Design
ASPEN: A Phase 3 Study of Zanubrutinib vs Ibrutinib in Waldenström’s Macroglobulinemia Study Design Primary endpoint: CR or VGPR, per modified IWWM6, by independent review Arm A Cohort 1: R/R or TN* WM with MYD88L265P mutation Secondary Endpoints: Zanubrutinib 1) MRR (>PR) 160 mg BID until PD 2) PFS
Slide 9: Efficacy Summary: Primary Endpoint Response Rate
Efficacy Summary Primary Endpoint Response Rate Relapsed or Refractory Overall Zanubrutinib Ibrutinib Zanubrutinib Ibrutinib (N = 83) (N = 81) (N = 102) (N = 99) CR 0 0 0 0 VGPR 24 (28.9) 16 (19.8) 29 (28.4) 19 (19.2) PR 41 (49.4) 49 (60.5) 50 (49.0) 58 (58.6) MR 13 (15.7) 11 (13.6) 17 (16.7) 15 (15
Slide 10: Efficacy Summary: Landmark PFS and OS
Efficacy Summary Landmark Data PFS and OS* Relapsed or Refractory Overall Zanubrutinib Ibrutinib Zanubrutinib Ibrutinib (N = 83) (N = 81) (N = 102) (N = 99) 6-month PFS, % 96.3 91.1 95.0 91.6 (CI) (88.9 - 98.8) (82.3 - 95.7) (88.4 - 97.9) (83.9 - 95.7) 12-month PFS, % 92.4 85.9 89.7 87.2 (CI) (83.8
Slide 11: Safety: Overall Summary
Safety: Overall Summary Overall Zanubrutinib Ibrutinib (N =101) (N = 98) Any Adverse Event (AE) 98 (97%) 97 (99.0%) Grade 3 or Higher AE 59 (58.4%) 62 (63.3%) Serious Adverse Event (SAE) 40 (39.6%) 40 (40.8%) Fatal AE 1 (1%) 4 (4.1%) AE Leading to Treatment Discontinuation 4 (4%) 9 (9.2%) AE Leading
Slide 12: Adverse Events of Special Interest
Adverse Events of Special Interest Overall Zanubrutinib Ibrutinib (N = 102) (N = 99) AEs of Interest, n, % Atrial fibrillation/flutter (all grades) 2 (2.0%) 15 (15.3%) Minor bleeding 49 (48.5%) 58 (59.2%) (bruising, contusion, petechiae) Major hemorrhage* 6 (5.9%) 9 (9.2%) Diarrhea (all grades) 21 (
Slide 13: ASPEN: Conclusions and Next Steps
ASPEN: Conclusions and Next Steps • In this Phase 3 study, the first randomized comparison of a highly-selective BTK inhibitor (zanubrutinib) with ibrutinib: ─ Statistical significance for the primary endpoint (VGPR or better) was not met ─ Clinically meaningful differences in safety favoring zanubr
Slide 14: BRUKINSA Development Update
BRUKINSA Development Update Eric Hedrick, M.D., Chief Advisor 14
Slide 15: Zanubrutinib Development Program
Zanubrutinib Development Program • Broad clinical trials program intended to support the approval of zanubrutinib in MCL, WM, CLL, MZL, and FL • Best-in-class hypothesis (safety and efficacy) is being tested in head-to-head trials versus ibrutinib in WM and CLL ─ Complete and sustained BTK occupancy
Slide 16: Brukinsa Broad Clinical Development Program
Brukinsa Broad Clinical Development Program Nine ongoing potentially registration-enabling studies Pivotal Phase 2 (n=86) in R/R MCL Filed, In NDA review zanu monotherapy, PE: ORR Phase 3 (n=500) in 1L MCL Phase 1/2 cohort (n=45) in MCL Initiated: Mar 2017, Enrollment complete: Sep 2017 R+zanu vs. R
Slide 17: Ongoing Global Phase 3 Studies in CLL/SLL
Ongoing Global Phase 3 Studies in CLL/SLL SEQUOIA and ALPINE Zanubrutinib vs. BR in 1L CLL/SLL Zanubrutinib vs. Ibrutinib in R/R CLL/SLL Cohort 1: Non–17p del TN CLL Arm A Must be not suitable for FCR Zanubrutinib Relapsed/Refractory CLL/SLL 160 mg BID until PD Arm A Previously (received ≥ 1 prior t
Slide 18: Zanubrutinib Near-Term Events
Zanubrutinib Near-Term Events • Broad clinical trial program continues in multiple indications • We plan to discuss ASPEN data with U.S. FDA and EMA • SEQUOIA Phase 3 study in 1L CLL (zanubrutinib vs BR): enrollment completed ─ Potential interim PFS analysis and top-line read out in 2020 • ALPINE Ph
Slide 19: BRUKINSA Commercial Update
BRUKINSA Commercial Update Josh Neiman, Head, U.S. Commercial 19
Slide 20: U.S. BRUKINSA Launch Progress
U.S. BRUKINSA Launch Progress BRUKINSA made commercially available within four days of November approval Josh Neiman Head, U.S. Commercial Flatiron Onyx Pharmaceuticals Genentech • patient support program launched within BRUKINSA™ (zanubrutinib) is minutes of approval approved in the U.S. for R/R MC
Slide 21: John V. Oyler, Chairman, Co-Founder & CEO
John V. Oyler Chairman, Co-Founder & CEO 21
Slide 22: Concluding Remarks
Concluding Remarks • Zanubrutinib’s broad program on track ─ Despite not reaching primary endpoint of superiority, ASPEN provides evidence suggesting differentiation in both efficacy and safety / tolerability for zanubrutinib in the first randomized comparative trial within the BTK inhibitor class.
Slide 23: Q&A
Q&A
Slide 24: Thank You
Thank You
Slide 25: Supporting Information
Supporting Information
Slide 26: ASH 2019 - SEQUOIA 1L CLL/SLL
ASH 2019 - SEQUOIA 1L CLL/SLL BRUKINSA VS Bendamustine Rituximab del(17p) Cohort 26
Slide 27: SEQUOIA Study Design
SEQUOIA Study Design NCT03336333 Arm A: zanubrutinib Cohort 1 open-label without del(17p) Key Eligibility R 1:1 n ~ 450 Arm B: bendamustine + rituximab • Treatment-naïve CLL/SLL • Met iwCLL criteria for zanubrutinib Requirement for Arm C Cohort 2 Arm C: treatment 160 mg bid until PD, Central assessm
Slide 28: Best Overall Response
Best Overall Response Investigator assessment Best Response, n (%) n = 109 Safety ORR (CR, PR, or PR-L), n (%) [95% CI]a 101 (92.7) [86.0-96.8] • 36.7% of patients (40/109) experienced CR 2 (1.9) at least one grade ≥3 adverse event (AE) PR 86 (78.9) and three patients discontinued PR-L 13 (11.9) tre
Slide 29: ASH 2019 - Global Phase 1/2 CLL/SLL Cohort
ASH 2019 - Global Phase 1/2 – CLL/SLL Cohort First in Human Study 29
Slide 30: AU-003 Study Schema
AU-003 Study Schema Indication-Specific Expansion Cohorts RP2D DOSE ESCALATION RP2Da 320 mg DOSE EXPANSION All Dosed BID 320 mg qd RP2D All Dosed Dose (CLL/SLL) Pop Disease or Dose (CLL/SLL) 40 mg qd 3 (0) 160 mg bid R/R qd All B-cell 18 (2) 80 mg qd 4 (0) R/R bid All B-cell 21 (4) 160 mg qd 5 (2) R
Slide 31: Disease Response by Investigator Assessment
Disease Response by Investigator Assessment R/R Overall TN (n=22) (n=101) (N=123) Overall Safety 31.7 (11.1- 24.3 (3.7- Follow-up, median (range), mo 29.5 (3.7-52.0) 47.6) 52.0) • 61.8% of patients (76/123) experienced at least one grade ≥3 AE and five Best response, n (%) patients discontinued trea
Slide 32: Disease Response: Patients With Del(17p)
Disease Response by Investigator Assessment Patients With Del(17p) Overall TN (n=3) R/R (n=13) (n=16) Overall Safety Follow-up, median 34.8 (31.8- 24.5 (9.4- 31.2 (9.4- • 61.8% of patients (76/123) experienced at (range), mo 35.3) 43.5) 43.5) least one grade ≥3 AE and five patients discontinued trea
Slide 33: Waldenström's Macroglobulinemia
Waldenström’s Macroglobulinemia 33
Slide 34: Zanubrutinib Efficacy in WM
Zanubrutinib Efficacy in WM Favorable response depth and durability Overall Response Rate (ORR) Progression Free Survival (PFS) Best Response in zanubrutinib WM Overall TN RR Evaluable for 73 24 49 efficacy, n 95% CI Median Follow-up 23.9 mo 12.3 mo 24.8 mo Mod. 6th IWWM Response Criteria (IgM decre
Slide 35: Ibrutinib Efficacy in WM
Ibrutinib Efficacy in WM Overall Response Rate (ORR) Progression Free Survival (PFS) Best Response ibrutinib Enrolled, n 63 100 Median Time-on-Treatment 19.1 months free 90 80 Modified 3rd IWWM 70 Response Criteria (IgM only) 60 50 Median Prior Lines of Tx 2 (1-9) 40 Survival (%) 30 20 ORR, n (%) 57
Slide 36: Mantle Cell Lymphoma
Mantle Cell Lymphoma 36
Slide 37: Zanubrutinib Efficacy in R/R MCL
Zanubrutinib Efficacy in R/R MCL From U.S. approved label Best Response Zanubrutinib RR RR Study BGB-3111-206 BGB-3111-AU-003 Source Ph2 study 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
Slide 38: CLL/SLL
CLL/SLL 38
Slide 39: Zanubrutinib Efficacy in CLL/SLL Phase 1/2
Zanubrutinib Efficacy in CLL/SLL Frequent and durable responses – Phase 1/2 Overall Response Rate (ORR) Progression Free Survival (PFS) zanubrutinib TN CLL R/R CLL Total CLL n 16 50 66 Median follow- - free 7.6 14.0 10.5 up (mo) Best Response ORR 16 (100%) 46 (92%) 62 (94%) CR 1 (6%) 1 (2%) 2 (3%) S
Slide 40: Zanubrutinib Efficacy in CLL/SLL Phase 2
Zanubrutinib Efficacy in CLL/SLL Frequent and durable responses – Phase 2 Best Overall Response by IRC (ORR) Progression Free Survival by IRC (PFS) zanubrutinib Total CLL n 91 Median follow-up (mo) 15.1 Best Response ORR 77 (84.6%) CR 3 (3.3%) PR 54 (59.3%) PR-L 20 (22.0%) SD 4 (4.4%) Non-evaluablea
Slide 41: Ibrutinib Efficacy in CLL/SLL
Ibrutinib Efficacy in CLL/SLL Overall Response Rate (Relapsed / Refractory) Progression Free Survival (Relapsed / Refractory) n 85 free Median FU (mo) 20.9 Best Response ORR 75 (88%) CR 2 (2%) PR 58 (68%) Survival PR-L 15 (18%) SD NR PD NR Probability - Progression of Probability Overall Response Ra
Slide 42: Follicular Lymphoma
Follicular Lymphoma 42
Slide 43: Zanubrutinib Plus Obinutuzumab in Follicular Lymphoma
Zanubrutinib Plus Obinutuzumab Combination in Follicular Lymphoma Data from separate trials Zanubrutinib + FL Zanubrutinib Ibrutinib Obinutuzumab Idelalisib Obinutuzumab Source ICML 20191 ASH 20172 ASH 20163 JCO 20134 NEJM 20145 n 36 17 110 34 72 prior alkylator and CD20, prior alkylator and CD20, m
Slide 44: Various B-cell Malignancies
Various B-cell Malignancies 44
Slide 45: Zanubrutinib Responses Across Additional B-Cell Malignancies
Zanubrutinib Responses Across Additional B-Cell Malignancies MZL MCL MCL FL FL DLBCL China CSCO Source ASH 20171 ICML 20193 pivotal data ASH 20171 ASH 20171 20184 ASH20182 n 9 48 85 17 26 26 Follow-up 7.0 mo 16.7 mo 35.9 wk 7.8 mo 9.5 mo 4.2 mo (med) Prior Lines 2 (1-8) 1 (1-4) 2 (1-4) 2 (1-8) 3 (1-
Slide 46: Pooled Safety
Pooled Safety 46
Slide 47: Pooled Safety Data
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] - [3.0]3 [1.9]3 Atrial fibrillation % ~2% 1.9%