Developing & Commercializing Targeted Small Molecule Drugs in Cancer

Transcription

1 Developing & Commercializing Targeted Small Molecule Drugs in Cancer Jefferies 2015 Healthcare Conference Ron Squarer, Chief Executive Officer November 19, 2015

2 Safe Harbor Statement Forward-looking statements made in the course of this presentation are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of The audience is cautioned that such forward looking statements involve risks and uncertainties, including those described in our annual report filed on form 10-K for the year ended June 30, 2015, and other filings of the Company with the Securities and Exchange Commission, which may cause the Company's actual results and experience to differ materially from anticipated results and expectations expressed in these forward-looking statements. 2

3 New Partnership Enhances Binimetinib & Encorafenib Value Broad global clinical program conducted with oncology powerhouse Novartis Three global Phase 3 trials nearing completion Top-line results from NEMO anticipated before the end of 2015 and from COLUMBUS in the first half of 2016 Multiple regulatory submissions planned in exploratory studies, including combinations with novel agents, on-going Trials designed to inform potential life-cycle opportunities Array s Selection Criteria for Strong European Commercial Partner was Met by Pierre Fabre Company with Europe as leading geographic priority with robust emerging market capability to provide scale to the collaboration Company with significant footprint in Oncology Development, Sales & Marketing Company willing to commit significant resources to ensure binimetinib & encorafenib success Company providing robust downstream economics (royalties) for ready-to-file products 3

4 Strategic Collaboration with Pierre Fabre Oncology Binimetinib & Encorafenib Pierre Fabre Oncology Pierre Fabre Oncology is supported by over 1,000 employees with a strong focus on European markets Focused on the discovery, development and commercialization of proprietary pharmaceuticals Significant commitment and track record in pharmaceutical R&D, developing products for patients afflicted with lung, breast and other solid tumors and hematological cancers 30 years of innovation with cancer therapeutics 2014 oncology sales surpassed $200 million on the strength of Oral Navelbine, Javlor and Busilvex Pierre Fabre Global healthcare company Headquartered in France 10,000 employees 37% international Subsidiaries in 43 countries 2014 global sales reached 2.1 billion across 130 countries Allocated 17% of 2014 pharmaceutical sales to R&D including oncology therapy 4

5 Strategic Collaboration with Pierre Fabre Oncology Summary of Deal Terms Benefits to Array $30 million upfront 40% funding for certain future clinical development Up to $425 million in potential development & commercialization milestones Robust, tiered double-digit royalties Commercialization Rights Array retains exclusive rights in: United States Canada Japan Korea Israel Pierre Fabre will have exclusive rights in all other geographies, including Europe, Asia & Latin America 5 The agreement remains subject to European Commission on Competition review and approval.

6 Binimetinib & Encorafenib Programs Significant Value to Array Novartis Responsibility Continues Conducting and/or substantially funding all ongoing trials Providing ongoing product supply and critical transition support for manufacturing Ensuring the NRAS and BRAF melanoma companion diagnostic program is seamlessly transitioned Providing access to several Novartis pipeline agents for combination studies including CDK 4/6 inhibitor and αpi3k inhibitor Joint Future Development with Pierre Fabre Costs split on a 60:40 basis (Array:Pierre Fabre) Initial funding of 100 million+ committed for new clinical trials in colorectal cancer and melanoma Value of Recent Novartis and Pierre Fabre Deals to Array Net cash impact: $137M ($85M Novartis upfront, $30M Pierre Fabre upfront, $22M Novartis extinguished net liabilities) Potential milestones: $425M (from Pierre Fabre) Royalty: Robust, tiered double-digit (from Pierre Fabre Sales) Wholly-Owned Commercial Rights: United States, Canada, Japan, Korea and Israel 6

7 Path to Commercialization Upcoming Catalysts for Binimetinib & Encorafenib 7 *Pivotal trial completed patient enrollment or reached target enrollment

8 ECC/ESMO NRAS mutant Melanoma

9 Binimetinib+Ribociclib (LEE011, CDK4/6) Ph. 1b/2 NRAS-mut. Melanoma Study Design Phase 1b/Dose Escalation Phase 2 Metastatic or Locally- Advanced NRAS-Mutant Melanoma N 15 Ribociclib + Binimetinib Two dosing regimens 28-day cycle (N = 22) a 21-day cycle (N = 23) b,c MTD and/or RP2D Metastatic or Locally- Advanced NRAS-Mutant Melanoma Treated at RP2D and Schedule (N 40) Phase 1b Doses and Schedule 9 Regimen 28-day cycle a 21-day cycle b,c Dose Level Ribociclib (mg QD) Binimetinib (mg BID) Patients, n a 28-day cycle = Binimetinib on a continuous dosing schedule. and ribociclib for 21 consecutive days followed by a 7-day planned break b 21-day cycle = Binimetinib and ribociclib both for 14 consecutive days each cycle followed by a 7-day planned break. c An additional dose level is now being tested in the 21-day cycle regimen (ribociclib 600 mg QD + binimetinib 45 mg BID) Investigational compound Ribociclib discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals

10 Binimetinib+Ribociclib 28-Day Regimen Promising Preliminary Clinical Activity in NRASm Mel. Response, n (%) All 28-day Regimen Patients (n = 22) All 21-day Regimen Patients (n = 23) Evaluable patients Complete response 0 0 Partial response (PR) Confirmed PR 5 (23) Unconfirmed PR 4 (18) 3 (14) 1 (5) Stable disease 9 (41) 11 (50) Progressive disease 3 (14) 4 (18) Unknown 1 (5) 3 (14) Overall response rate a 9 (41) 4 (18) Disease control rate a 18 (82) 15 (68) Median PFS, months *Patients with confirmed PR. Patients with prior immunotherapy treatment. a Rate includes unconfirmed CR/PR. Data cut off, June 5, Individual Patient Responses Phase 3 trial binimetinib (single agent) advancing in NRAS mutant melanoma (NEMO); projected regulatory filing 2016 Potential for binimetinib beyond single agent in combinations NRAS mutant melanoma has poor prognosis with no approved targeted therapies 10 ECC/ESMO 2015: A phase 1b/2 study of ribociclib (LEE011; CDK4/6 inhibitor) in combination with binimetinib (MEK162; MEK inhibitor) in patients with NRAS-mutant melanoma naive to BRAFi treatment (Abstract #3300)

11 Binimetinib+Ribociclib 28-Day Regimen Safety Profile in NRAS-mut. Melanama Adverse Events Regardless of Causality ( 30% of All Patients) Adverse Event, n (%) RIBO 200 mg + BINI 45mg (n = 9) RIBO 250 mg + BINI 45 mg (n = 3) RIBO 300 mg + BINI 30 mg (n = 4) RIBO 300 mg + BINI 45 mg (n = 6) All Patients (N = 22) All Gr Gr 3/4 All Gr Gr 3/4 All Gr Gr 3/4 All Gr Gr 3/4 All Gr Gr 3/4 Total 9 (100) 9 (100) 3 (100) 2 (67) 4 (100) 3 (75) 6 (100) 6 (100) 22 (100) 20 (91) Blood CPK increased 6 (67) 1 (11) 2 (67) 0 3 (75) 1 (25) 4 (67) 2 (33) 15 (68) 4 (18) Nausea 5 (56) 3 (33) 2 (67) 0 3 (75) 0 4 (67) 0 14 (64) 3 (14) Vomiting 4 (44) 2 (22) 3 (100) 0 4 (100) 0 3 (50) 0 14 (64) 2 (9) Diarrhea 4 (44) 0 2 (67) 0 2 (50) 0 4 (67) 0 12 (55) 0 Peripheral edema 4 (44) 0 2 (67) 0 2 (50) 0 3 (50) 1 (17) 11 (50) 1 (5) Anemia 3 (33) 1 (11) 2 (67) 0 2 (50) 0 4 (67) 1 (17) 11 (50) 2 (9) Fatigue 5 (56) 1 (11) 1 (33) 0 3 (75) (41) 1 (5) Dermatitis acneiform 6 (67) 0 1 (33) 1 (33) (33) 0 9 (41) 1 (5) Constipation 3 (33) 0 1 (33) 0 2 (50) 0 3 (50) 1 (17) 9 (41) 1 (5) Hypoalbuminemia 4 (44) 1 (11) 2 (67) 0 1 (25) 0 2 (33) 1 (17) 9 (41) 2 (9) AST increased 4 (44) 1 (11) 1 (33) 0 1 (25) 0 2 (33) 0 8 (36) 1 (5) Hypomagnesemia 4 (44) (25) 0 3 (50) 0 8 (36) 0 Blood LDH increased 4 (44) 0 1 (33) 0 2 (50) 0 1 (17) 0 8 (36) 0 Hyperphosphatemia 4 (44) 0 1 (33) 0 1 (25) 0 1 (17) 0 7 (32) 0 Blood creatinine increased 1 (11) 0 2 (67) 0 2 (50) 0 2 (33) 0 7 (32) 0 Data cut off, June 5, ECC/ESMO 2015: A phase 1b/2 study of ribociclib (LEE011; CDK4/6 inhibitor) in combination with binimetinib (MEK162; MEK inhibitor) in patients with NRAS-mutant melanoma naive to BRAFi treatment (Abstract #3300)

12 ECC/ESMO BRAF mutant Melanoma

13 Binimetinib+Encorafenib+Third Agent - LOGIC2 BRAF Melanoma Study Design Patient enrollment on-going N=140 PART 1 n=89 as of 7/1/15 PART 2 n=20 as of 7/1/15 Group A BRAF- & MEK-naïve patients Group B Patients with any BRAF/MEK combo or single agents (non-naïve) Group C Patients prev. in Columbus, LOGIC1, CMEK162X2110, or Group A (non-naive) Group A Binimetinib + Encorafenib Group B Run-in Binimetinib + Encorafenib Group C Optional Binimetinib + Encorafenib Primary endpoint: Overall Response Rate (Part 2) Secondary endpoint: Safety After progressive disease, genetic assessment performed to determine combination Binimetinib + Encorafenib+LEE011 (CDK 4/6 inhibitor) Binimetinib + Encorafenib+ BGJ398 (pan FGFR inhibitor) Binimetinib + Encorafenib+ BKM120 (pan PI3K inhibitor) Binimetinib + Encorafenib+INC280 (c-met inhibitor) After PD in Part 1: Tumor biopsy genetic assessment performed to determine combination treatment in Part 2 13 Part 2 Third agent: LEE011 (CDK 4/6 inhibitor), BGJ398 (pan FGFR inhibitor), BKM120 (pan PI3K inhibitor) or INC280 (c-met inhibitor)

14 LOGIC2 Binimetinib+Encorafenib (Part 1) - Encouraging Preliminary Clinical Activity Phase 2 (NCT ) 1 BRAF-mutant melanoma (as of 7/1/15) Objective Response Rate (ORR) 2, 3 68% Disease Control Rate (DCR) 2, 4 95% Binimetinib 45mg BID / Encorafenib 450mg QD BRAFi/MEKi naïve patients (n=40) 6-month Median Progression Free Survival 79% Note: 96% of patients continued to receive study treatment as of data cutoff Complete response (CR) 2 3% (1) Partial response (PR) 2 65% (26) Stable disease (SD) 28% (11) Combination of Binimetinib and Encorafenib Demonstrated Encouraging Preliminary Clinical Activity in BRAFi/MEKi Naïve Patients 14 1 ECC/ESMO 2015: LOGIC2: Phase 2, multi-center, open-label study of sequential encorafenib/binimetinib combination followed by a rational combination with targeted agents after progression, to overcome resistance in adult patients with locally-advanced or metastatic BRAF V600 melanoma (Abstract #3310) 2 Includes confirmed/unconfirmed responses, 3 ORR=CR/PR, 4 DCR=CR/PR or SD

15 LOGIC2 Binimetinib+Encorafenib (Part 1) - Good Tolerability Phase 2 (NCT ) (as of 7/1/15) AE, n (%) Group A (MEKi + BRAFi naïve) ENCO 450mg QD + BINI 45mg BID n=45 All Grades n (%) Grade 3/4 n (%) Group B (Prior BRAFi and/or MEKi) ENCO 450mg QD + BINI 45mg BID n=43 All Grades n (%) Grade 3/4 n (%) All Patients N=89 All Grades n (%) Grade 3/4 n (%) Total 42 (93) 16 (36) 39 (91) 21 (49) 82 (92) 37 (42) Nausea 12 (27) 3 (7) 12 (28) 2 (5) 24 (27) 5 (6) Diarrhea 14 (31) 0 8 (19) 0 23 (26) 0 Fatigue 9 (20) 1 (2) 12 (28) 2 (5) 22 (25) 3 (3) Retinopathy 14 (31) 0 7 (16) 0 21 (24) 0 Vomiting 7 (16) 1 (2) 7 (16) 0 15 (17) 1 (1) Blood CPK increased 11 (24) 1 (2) 3 (7) 0 14 (16) 1 (1) Pyrexia 5 (11) 1 (2) 6 (14) 0 11 (12) 1 (1) Abdominal Pain 7 (16) 0 3 (7) 0 10 (11) 0 Anemia 4 (9) 1 (2) 6 (14) 3 (7) 10 (11) 4 (5) Vision blurred 5 (11) 0 4 (9) 0 9 (10) 0 Differentiated Safety: 12% pyrexia, 7% rash & no photosensitivity Data cutoff date: July 1, CPK: creatine phosphokinase

16 Published MEK/BRAF in BRAF-mutant Melanoma Safety Profile & Clinical Activity Trametinib + dabrafenib 1 NOV COMBI-D (n=209) Trametinib + dabrafenib 2 NOV COMBI-V (n=350) Cobimetinib + vemurafenib 3 Roche - cobrim (n=247) Fever 52% 55% 28% Rash 24% 24% 16% SELECT ADVERSE EVENTS OF INTEREST Diarrhea Chills 18% 34% 28% 33% 60% 10% Hypertension 10% 29% 15% Photosensitivity NR (<10%) 4% 46% NR = Not Reported COMBI-D (n=210) COMBI-V (n=351) cobrim 4 (n=247) ORR (CR + PR) BRAFi naive 69% 66% 70% 16 1 Long et al ASCO Oral 2015; 2 ESMO/ECC 2015 ; 3 Product label; 4 Larkin et al ASCO Oral 2015

17 ESMO GI BRAF-mutant Colorectal Cancer

18 Encorafenib - Ph. 2 BRAF-mut. mcrc Encouraging Clinical Activity ENC + CTX (n = 42) ENC + ALP (BYL719, PI3K inhib.) + CTX (EGFR inhib.) (n = 49) Evaluable patients a PR 11 (29%) b 15 (35%) c SD 20 (53%) 19 (44%) PD 1 (3%) 3 (7%) Unknown 6 (16%) 6 (14%) Overall response rate 11 (29%) b 15 (35%) c DCR 31 (82%) 34 (79%) Historically, response rates are very low for either single-agent EGFR or RAF inhibitor therapy in patients with BRAF-mut. CRC. Data in this study suggest a synergistic effect for the combination of encorafenib and cetuximab in this population. 18 Data cutoff date: May 22, a Evaluable patients had a tumor assessment at the 12 week visit or later and/or started treatment 13 weeks prior to data cutoff. b Includes 4 unconfirmed PRs. c Includes 5 unconfirmed PRs. CR and PR were confirmed by repeat assessments performed 4 weeks after initial response.

19 Encorafenib - Ph. 2 BRAF-mut. mcrc Good Tolerability ENC + CTX (n = 42) ENC + ALP + CTX (n = 49) AE, n (%) All Grades Grade 3/4 All Grades Grade 3/4 Total 37 (88%) 12 (29%) 46 (94%) 24 (49%) Diarrhea 9 (21%) 1 ( 2%) 19 (39%) 4 ( 8%) Nausea 13 (31%) 0 18 (37%) 3 ( 6%) Fatigue 15 (36%) 0 16 (33%) 3 ( 6%) Hyperglycemia 1 ( 2%) 0 15 (31%) 7 (14%) Rash 7 (17%) 0 13 (27%) 0 Stomatitis 4 (10%) 0 13 (27%) 2 ( 4%) Decreased appetite 9 (21%) 0 11 (22%) 1 ( 2%) Pruritus 7 (17%) 0 11 (22%) 0 Dry skin 5 (12%) 0 10 (20%) 0 Maculopapular rash 1 ( 2%) 0 10 (20%) 2 ( 4%) Lipase increased 10 (24%) 7 (17%) 4 ( 8%) 2 ( 4%) Across all treatment groups, most AEs were Grade 1 or 2 Data cutoff date: May 22,

20 Published BRAF in BRAF-mutant mcrc Safety Profile & Clinical Activity Panitumumab+Dabrafenib a Novartis Phase 2 (n=20) Panitumumab+Dabrafenib +Trametinib a Novartis Phase 2 (n=35) ORR (CR + PR) 10% 26% No Doublet Included Cetuximab+vemurafenib+ Irinotecan b Roche Phase 1 (n=18) 35% Fatigue 45% 51% 94% SELECT ADVERSE EVENTS OF INTEREST Nausea Diarrhea 40% 45% 49% 77% 83% 89% Rash 30% 37% 78% Pyrexia 40% 46% Not reported Doublet Therapy Triplet Therapy 20 a ESMO GI 2015, b ASCO 2015 Panitumumab: EGFR inhibitor, Dabrafenib: Raf inhibitor, Trametinib: MEK inhibitor Cetuximab: EGFR inhibitor, Vemurafenib: Raf inhibitor, Irinotecan: Cytotoxic

21 Catalysts

22 Array Expected Product Portfolio Calendar 2015 Value Drivers BINIMETINIB & ENCORAFENIB BINIMETINIB ENCORAFENIB DRUG INDICATION(S) STATUS Binimetinib (MEK162) Encorafenib (LGX818) Binimetinib (MEK162) Encorafenib (LGX818) BRAF Melanoma PH 3 NRAS Melanoma LGS Ovarian Cancer PH 3 BRAF Colorectal Cancer PH 2 Q1 Q2 Q3 Q4 NEMO enrolled MILO enrollment ongoing COLUMBUS Part 1 enrolled BRAF-mel. data / ASCO BRAF CRC data COLUMBUS Part 2 target enrollment complete LOGIC-2 / BRAF-mel. data / ECC/ESMO 2015 NEMO top-line results / Q4 NRAS melanoma combo. data / ECC/ESMO 2015 BRAF CRC lifecycle SELUMETINIB Selumetinib (AZD6244) (AstraZeneca) NSCLC Thyroid Cancer NF1 PH 3 ARRY-797 ARRY-797 LMNA-related DCM PH 2 SELECT-1 enrollment ongoing ASTRA enrollment ongoing NF1 data Additional results Registration trials in NF-1 advancing Filanesib Filanesib Multiple Myeloma PH 2 Single-agent & Kyprolis-combo Phase 2 trials nearing completion No plans to initiate additional trials with filanesib 22 ECC/ESMO 2015: European Cancer Congress, September 2015 MILO: MEK Inhibitor in Low Grade Serous Ovarian Cancer; NEMO: NRAS melanoma and MEK inhibitor; COLUMBUS: Combination of LGX818 used with MEK162 in BRAF mutant unresectable skin cancer; ASTRA: Pivotal trial in differentiated thyroid cancer ; SELECT-1: Selumetinib + Docetaxel in Patients with KRAS NCSLC

23 Inventing, Developing & Commercializing Targeted Small Molecule Drugs in Cancer 23