ARRAY BioPharma. September > Founded on Science, Focused on Patients

Transcription

1 ARRAY BioPharma September 2018 > Founded on Science, Focused on Patients 1

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, 2018, 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 Maximizing Success of Encorafenib & Binimetinib is Array s Top Priority FDA Approved BRAFTOVI (encorafenib) + MEKTOVI (binimetinib) June 2018 SIGNIFICANT MILESTONES ACHIEVED BRAFTOVI + MEKTOVI launched in US Positive reception from U.S. melanoma healthcare providers NCCN guidelines recommend BRAFTOVI + MEKTOVI as first-line treatment option for patients with metastatic or unresectable melanoma with a BRAF V600- activating mutation BRAFTOVI + MEKTOVI receives positive CHMP opinion for advanced BRAF-mutant melanoma snda submitted to seek inclusion of OS data in BRAFTOVI + MEKTOVI label PHASE 3/BRAF-MUTANT CRC FDA granted Breakthrough Therapy Designation Plan to amend BEACON CRC protocol to allow for interim analysis based on consultation with FDA and EMA; analysis for U.S. snda based primarily on ORR and duration of response Promising activity in safety lead-in reported at ESMO World GI 2018 At the time of analysis, mos not yet reached; OS mature through 12.6 months; 62% one-year OS rate Binimetinib + I/O COLLABORATIONS/MSS CRC AND OTHER CANCERS WITH IMPORTANT UPCOMING VALUE DRIVERS Marketing applications in Europe and Japan under review Complete enrollment expected around end of the year Plan to seek accelerated approval in the U.S. based on positive results Topline results 1H19 COST SHARING BEACON CRC co-funding: Pierre Fabre (40%), Ono Pharmaceuticals (milestone payments), Merck KGaA (Erbitux supply) BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDAapproved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; **Pharmaceuticals and Medical Devices Agency, Japan; ǂBEACON CRC trial safety data available on slide 24; RAS mutant. Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: National Comprehensive Cancer Network, Inc To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 3

4 BRAFTOVI + MEKTOVI Approved for BRAF-mutant Melanoma BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the U.S. for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Encorafenib (BRAFTOVI) + binimetinib (MEKTOVI) added to NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines ) for melanoma Category 1 recommendation, National Comprehensive Cancer Network (NCCN ): Encorafenib (BRAFTOVI) + binimetinib (MEKTOVI) is a recommended 1 st -line treatment option for patients with metastatic or unresectable melanoma with a BRAF V600 -activating mutation. 1 1 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) for Melanoma V National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 12, To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma. Important safety information available on slides Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 4

5 BRAFTOVI + MEKTOVI LAUNCH: POSITIVE EARLY RECEPTION KEY EVENTS Launched within days of approval Label reflects attractive and differentiated offering for BRAFmutant advanced melanoma patients Strong reception from the melanoma community, especially academic cancer centers Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 5

6 Encorafenib & Binimetinib Well-Positioned for Success Partnerships with Ono Pharmaceutical & Pierre Fabre Create a Strong Global Footprint U.S. EUROPE JAPAN Other: Canada, Israel ROW South Korea Upfront & Milestone Payments: Global Development Co-Funding: Remaining Milestones: $30 million $35 million 40% 12% $415 million $148 million* Royalties: Max. 35% above 100M combined annual sales Max. 25% above 10B combined annual sales *Exchange rate as of the most recent quarter end 6

7 Robust Development Pipeline Following BRAFTOVI + MEKTOVI 6 Partnered Programs In Registration Trials, 2 Wholly-owned Clinical Programs Advancing Compound (Partner) Disease State Target Phase 1 Phase 2 Phase 3 / Registration Trial BRAFTOVI + MEKTOVI * (Ono, PF) Advanced BRAF-mutant melanoma BRAF + MEK Encorafenib (Ono, PF) BRAF-mutant CRC BRAF Binimetinib (Ono, PF) BRAF-mutant CRC & other cancers MEK Selumetinib (AstraZeneca) Thyroid Cancer and NF1 MEK Approved Approved in US Ganovo (danoprevir, Roche / Ascletis) Hepatitis C NS3 Protease Approved in China Larotrectinib (Loxo Oncology) Cancer PanTrk Tucatinib (Seattle Genetics) Breast Cancer HER-2 Ipatasertib (Genentech) Cancer AKT Varlitinib (ASLAN) Cancer Pan-HER ARRY-797 LMNA-dilated DCM p38 ARRY-382 Cancer CSF1R Motolimod (Celgene) Cancer TLR Prexasertib (Eli Lilly) Cancer Chk-1 LOXO-292 (Loxo Oncology) Cancer Ret GDC-0575 (Genentech) Cancer Chk-1 Wholly-owned US Wholly-owned Global Collaboration LOXO-195 (Loxo Oncology) Cancer Trk AK-1830 (Asahi Kasei Pharma) Inflammation Trk *BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma. Important Safety Information available on slides Other than the approval of BRAFTOVI and MEKTOVI for BRAF-mutant melanoma, these compounds and their uses are investigational and have not been approved by the FDA. This information is presented for the purposes of providing a general overview of our clinical trials only. 7

8 COLUMBUS Phase 3 Trial 8

9 COLUMBUS Phase 3 Results BRAFTOVI + MEKTOVI DEMONSTRATED mos OF 33.6 MONTHS* mos 33.6 months vs months, HR (0.61), [95% CI ], p<0.0001** PRIMARY ENDPOINT: BRAFTOVI + MEKTOVI SIGNIFICANTLY IMPROVED PFS COMPARED WITH VEMURAFENIB ALONE** mpfs 14.9 months vs. 7.3 months, HR (0.51), [95% CI ], p< SAFETY/TOLERABILITY OF BRAFTOVI + MEKTOVI*** Generally well-tolerated & reported AEs were overall consistent with previous ENCO/BINI combination clinical trial results in BRAF-mutant melanoma patients Grade 3/4 AEs that occurred in more than 5% of patients receiving BRAFTOVI + MEKTOVI were increased GGT (9%), increased blood CK (7%) and hypertension (6%) The incidence of selected any grade of AEs based on toxicities commonly associated with commercially available MEK+BRAFinhibitor treatments included: rash (22%) serous retinopathy (20%) pyrexia (18%) photosensitivity (5%) ENCO=encorafenib; BINI=binimetinib; CI=confidence interval; BRAFTOVI + MEKTOVI=encorafenib 450 mg daily and binimetinib 45 mg twice daily. *Dummer et al, ASCO Annual Meeting 2018; **All secondary efficacy analyses, including overall survival, are descriptive in nature; ***Dummer et al., The Lancet Oncology 2018; ǂCOLUMBUS trial design is described in Dummer et al., The Lancet Oncology 2018 BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma. Important safety information available on slides Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 9

10 Limited Use of Post-Trial Immunotherapy Consistent with other published pivotal trials of BRAF and MEK inhibitors in BRAF-mutant advanced melanoma TREATMENT RECEIVED AFTER STUDY DRUG 1 BRAFTOVI + MEKTOVI n=192 ENCO300 n=194 VEM n=191 Any treatment 42% 56% 62% Anti PD-1/anti PD-L1 20% 21% 25% Anti CTLA-4 17% 16% 19% Anti CTLA-4 + anti PD-1/anti PD-L1 3% 2% 2% BRAFi + MEKi 5% 14% 20% BRAFi 6% 8% 13% Chemotherapy 7% 12% 12% Other 3% 2% 7% BRAFi=BRAF inhibitor; BRAFTOVI + MEKTOVI=encorafenib 450 mg QD + binimetinib 45 mg BID; CTLA-4=cytotoxic T-lymphocyte-associated protein 4; ENCO300=encorafenib 300 mg QD; MEKi=MEK inhibitor; PD-1=programmed death 1; PD-L1=programmed death ligand 1; VEM=vemurafenib 960 mg BID. *Multiple uses of a therapy in a single patient were only counted once in the frequency for that category of therapy; patients who received multiple categories of therapy are counted in each respective row. COLUMBUS trial safety data available on slide Dummer et al, ASCO 2018 BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma. Important safety information available on slides Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 10

11 Historical Median Overall Survival Benchmarks in BRAF-Mutant Melanoma* BRAF+MEK Targeted Therapy Vemurafenib + cobimetinib 35 Dabrafenib + trametinib Vemurafenib Dabrafenib Months cobrim COMBI-D COMBI-V *Array has not conducted head-to-head studies comparing encorafenib and binimetinib against the other BRAF/MEK combination therapies, and these data come from separate Phase 3 studies. These trials were conducted under varying conditions and results may not be directly comparable. cobrim (NCT ) = vemurafenib+cobimetinib vs. vemurafenib+placebo; Lancet Oncol 2016; 17: COMBI-D (NCT ) = dabrafenib+trametinib vs. dabrafenib+placebo; Tafinlar and Mekinist prescribing information Revised 6/2017 COMBI-V (NCT ) = dabrafenib+trametinib vs. vemurafenib; Lancet 2015; 386: Tafinlar (dabrafenib) & Mekinist (trametinib) are registered trademarks of Novartis Pharma AG BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma. Important safety information available on slides Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 11

12 Projected Annual Revenue of Tafinlar + Mekinist Trending to Exceed $450M in U.S. & $1B Globally $ millions $300 $250 $200 $150 $100 QUARTERLY REVENUES Novartis Reported Financial Results: Net Sales Tafinlar /Mekinist HIGHLIGHTS Approx. 50% of advanced melanoma patients have activating BRAF mutations >29,000 individuals succumb to melanoma each year across the U.S., Europe & Japan Projected Tafinlar+Mekinist rolling annual revenue trending to exceed $450M in U.S. and >$1B globally 28% YOY growth in the U.S. & 36% globally $50 $0 1Q15 2Q15 3Q15 4Q15 1Q16 2Q16 3Q16 4Q16 1Q17 2Q17 2Q17 2Q17 1Q18 2Q18 U.S. US Global Global Quarterly Revenues (Tafinlar+Mekinist BRAFm NSCLC approved in April in EU & June in U.S.) Tafinlar (dabrafenib) & Mekinist (trametinib) are registered trademarks of Novartis Pharma AG 12

13 COLUMBUS Trial Design PART 1, n=577 (1:1:1 Randomization) PART 2, n=344 (3:1 Randomization) Patients with BRAF V600E/V600K advanced, unresectable or metastatic melanoma n = 921 Randomization Stratification Stage Performance Status Prior Immunotherapy MEKTOVI (45 mg) + BRAFTOVI (450mg) n=192 Vemurafenib n=191 Encorafenib (300mg) n=194 COMBO300 Binimetinib (45 mg) + Encorafenib (300mg) n=258 Encorafenib (300mg) n= 86 Primary Endpoint: Progression Free Survival (PFS) comparison of BRAFTOVI + MEKTOVI vs. vemurafenib Secondary Endpoints: PFS BRAFTOVI + MEKTOVI vs. encorafenib, PFS COMBO300 vs. encorafenib, Overall Survival BRAFTOVI + MEKTOVI vs. vemurafenib, Objective Response Rate, Safety Endpoints, QoL 13

14 DOSE EXPOSURE Duration of exposure, weeks BRAFTOVI + MEKTOVI n=192 BRAFTOVI MEKTOVI ENCO300 n=192 VEM n=186 Mean (SD) 54.3 (30.9) 53.8 (31.3) 42.4 (31.2) 35.9 (29.5) Median (range) 51.2 ( ) 50.6 ( ) 31.4 ( ) 27.1 ( ) 60 Relative Dose Intensity <50% 50 to <80% 80 to <100% 100% Percentage BRAFTOVI MEKTOVI ENCO300 VEM BRAFTOVI + MEKTOVI Median (range) dose intensity, % ( ) 99.6 ( ) 86.2 ( ) 94.5 ( ) BRAFTOVI + MEKTOVI =BRAFTOVI 450 mg daily + MEKTOVI 45 mg twice daily; ENCO=encorafenib; VEM=vemurafenib. Includes only patients receiving 1 dose of study drug. COLUMBUS trial safety data available on slide

15 OVERALL SUMMARY OF SAFETY Event BRAFTOVI + MEKTOVI n=192 Median Duration of Exposure: 51 weeks ENCO300 n=192 Median Duration of Exposure: 31 weeks VEM n=186 Median Duration of Exposure: 26 weeks Adverse events 98% 99% 100% Grade 3/4 adverse events 64% 67% 66% Adverse events leading to discontinuation 15% 15% 17% Adverse events leading to dose reduction/interruption 53% 71% 62% On-treatment deaths* 12% 8% 11% BRAFTOVI + MEKTOVI =BRAFTOVI 450 mg daily + MEKTOVI 45 mg twice daily; ENCO=encorafenib; VEM=vemurafenib. *Includes on-treatment deaths and deaths within 30 days of stopping study treatment. 15

16 PHASE 3 BRAF-MUTANT CRC TRIAL ADVANCING Promising BEACON CRC Safety Lead-In Activity 16

17 FDA Grants Breakthrough Therapy Designation Regulatory Update BREAKTHROUGH THERAPY DESIGNATION FDA has granted Breakthrough Therapy Designation for BRAFTOVI, in combination with MEKTOVI and cetuximab for the treatment of patients with BRAF V600E -mutant mcrc as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease. Breakthrough Therapy Designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition where preliminary clinical evidence indicates that they may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. REGULATORY UPDATE Plan to amend BEACON CRC protocol to allow for interim analysis based on consultation with FDA and EMA and to seek accelerated approval in the U.S. based on positive results Analysis for U.S. snda based primarily on ORR and duration of response Topline results anticipated in the first half of Timing allows for the subset of patients required for the interim analysis of ORR to achieve an objective response and for the durability of responses to be appropriately evaluated. BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; ǂ BEACON CRC trial safety data available on slide 24. Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 17

18 Phase 3 BRAF-mutant Colorectal Cancer Study Design Potential to Establish MEK + BRAF + EGFR Combination as New Standard of Care Currently Enrolling SAFETY LEAD-IN COMPLETE Safety and tolerability will be assessed in patients receiving binimetinib, encorafenib and cetuximab for the treatment of BRAF V600E-mutant metastatic colorectal cancer n=30 RANDOMIZED PORTION Patient population BRAF V600E mutant >65% 2 nd -line patients <35% 3 rd -line patients n=615 Randomization Triplet Therapy Binimetinib + Encorafenib + Cetuximab n=205 Doublet Therapy Encorafenib + Cetuximab n=205 Control Arm FOLFIRI + Cetuximab or irinotecan + Cetuximab n=205 DISEASE PROGRESSION DISEASE PROGRESSION DISEASE PROGRESSION Continued follow-up for evaluation of OS Primary Endpoint: Overall survival (OS) of the triplet therapy compared to the control arm Secondary Endpoints: Address efficacy of the doublet therapy compared to the control arm, and the triplet therapy compared to the doublet therapy Other Secondary Endpoints: Progression-free survival (PFS), objective response rate (ORR), duration of response, safety and tolerability. Health related quality of life data will also be assessed The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed in The use of encorafenib and binimetinib in this disease state is investigational only and has not been approved by the U.S. Food and Drug Administration. BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; ǂBEACON CRC trial safety data available on slide 24. Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 18

19 Observed Clinical Activity from BEACON CRC Safety Lead In and Certain Separate Historical Benchmarks in 2 nd Line+ BRAFm mcrc 2 ND Line+ BRAFm mcrc* ORR mpfs mos 48% 16 to 21% 4 to 8% to to ** 9.1 to to 6 Encorafenib, binimetinib + cetuximab 6 2 nd Line+ Safety Lead-In BRAF inhibitorcontaining triplet regimens 1,2 Irinotecan and cetuximabcontaining regimens 3-9 Encorafenib, binimetinib + cetuximab 6 2 nd Line+ Safety Lead-In BRAF inhibitorcontaining triplet regimens 1,2 Irinotecan and cetuximabcontaining regimens 3-9 Encorafenib, binimetinib + cetuximab 6 2 nd Line+ Safety Lead-In BRAF inhibitorcontaining triplet regimens 1,2 Irinotecan and cetuximabcontaining regimens 3-9 BRAF inhibitor-containing triplet regimens: dabrafenib, a BRAF inhibitor, trametinib, a MEK inhibitor and panitumumab, a monoclonal EGFR antibody or vemurafenib, a BRAF inhibitor, cetuximab and irinotecan, a chemotherapy *Array has not conducted head-to-head studies comparing encorafenib and binimetinib against the other BRAF/MEK combination therapies, and these data come from separate Phase 3 and Phase 2 studies. These trials were conducted under varying conditions and results may not be directly comparable. 1.Corcoran et al., Cancer Discovery April Kopetz et al., ASCO De Roock et al., Lancet Oncol, Ulivi et al., J Transl Med Peeters et al., ASCO Saridaki et al., PLoS One Loupakis et al., Br J Cancer Seymour et al., Lancet Oncol, 2013 (supplementary appendix) 9. Peeters et al., ASCO Van Cutsem et al, ESMO World GI 2018 **Median not yet reached; data mature through 12.6 months. BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; ǂ BEACON CRC trial safety data available on slide 24; Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 19

20 BEACON CRC Safety Lead-In 1 62% Observed Overall Survival at 1 Year; Median Overall Survival (mos) was not reached Overall survival (%) mos: Not reached Data fully mature through 12.6 months* * All patients have either died or have follow-up through 12.6 months. 1-year OS rate: 62% 10 0 Patients with BRAF V600 mutation (N=29) Censored patients Patients at risk Time (mo) Van Cutsem et al, ESMO World GI 2018 The use of encorafenib and binimetinib in this disease state is investigational only and has not been approved by the U.S. Food and Drug Administration. BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; ǂBEACON CRC trial safety data available on slide 24. Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 20

21 BEACON CRC Safety Lead-In 1 CONFIRMED BEST OVERALL RESPONSE* CR + PR PATIENTS (N=29)** N (%) 14 (48) (95% CI 29%-67%) 48% confirmed ORR (CR + PR) in patients with BRAF V600E mcrc CR 3 (10) 3 Complete Responses PR 11 (38) SD 13 (45) PD 0 Confirmed ORR for patients with 1 and 2 prior regimens were 62% and 31%, respectively DCR 27 (93) No postbaseline tumor assessments 2 (7) A BRAF V600E mutation was identified in 29 patients; 1 treated patient was determined to have a non-v600 BRAF mutation (BRAF G466V ) *Locally assessed response per RECIST 1.1; **Patients with BRAF V600E mutations; Nonresponders per intent-to-treat analysis; CR=complete response; PD=progressive disease; PR=partial response; SD=stable disease; DCR = Disease Control Rate; 1 Van Cutsem et al, ESMO GI 2018 BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; ǂBEACON CRC trial safety data available on slide 24. Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 21

22 BEACON CRC Safety Lead-In 1 Out of 28 patients with both BRAF V600E -mutant mcrc and a post-baseline assessment, 27 showed tumor regression 100 Tumor Regression reported in SWOG S Cetuximab + Irinotecan Treatment Arm Best % Change from Baseline RECIST ORR Criteria Stable Disease or Partial Response Partial Response (n=11) Complete Response (n=3) 27 out of 28 patients with a post-baseline assessment showed tumor regression and none showed RECIST-defined progression as their best response Preliminary estimate of mpfs is 8.0 months (95% CI, months) mpfs was similar between patients who had 1 vs 2 previous regimens (median, 95% CI, 8.0 [ ] vs 8.1 [ ] months) * * * Patients mcrc=metastatic colorectal cancer. *Patients with lymph node disease with decreases in short axis dimensions consistent with RECIST 1.1 defined Complete Response. One patient had no baseline sum of longest diameters and is not presented. 1Van Cutsem et al, ESMO GI 2018; 2Kopetz S, et al. J Clin Oncol. 2017;35:Abstr 3505, with permission. BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; ǂBEACON CRC trial safety data available on slide 24. Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 22

23 BEACON CRC Safety Lead-In 1 Duration of Exposure by Number of Prior Regimens Individual Patients* Prior Regimen (n=16) 2 Prior Regimens (n=13) Still on Treatment First Response Duration of Exposure (mo) *Patients BRAFV600E mutations; 1Van Cutsem et al, ESMO GI 2018 BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; ǂBEACON CRC trial safety data available on slide 24. Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 23

24 BEACON CRC Safety Lead-In 1 Safety PATIENTS (N=30) Adverse Events (AEs) 30 (100%) Grade 3/4 AEs 21 (70%) AEs leading to discontinuation* 6 (20%) AEs leading to dose 5 (17%) interruption/change On-treatment deaths 5 (17%) GRADE 3/4 AES REPORTED IN AT LEAST 10% OF PATIENTS WERE: Fatigue (4) Anemia (3) Increased blood creatine phosphokinase (CK; 3) Increased aspartate aminotransferase (AST; 3) *Includes increased blood bilirubin (1 patient), drug hypersensitivity (1 patient), dyspnea (1 patient), fatigue (1 patient), hypersensitivity (1 patient), malaise (1 patient), retinal detachment (1 patient). Discontinuation or dose interruption/change of at least one study drug. Includes on-treatment deaths and deaths within 30 days of stopping study treatment. On-treatment deaths were due to disease progression.1van Cutsem et al, ESMO GI 2018 BRAFTOVI capsules in combination with MEKTOVI tablets is approved in the US for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDAapproved test. Encorafenib and binimetinib are not approved for use in any other disease state. *Important Safety Information available on slides and COLUMBUS trial safety data available on slide 9; ǂBEACON CRC trial safety data available on slide 24. Please see full U.S. prescribing information for BRAFTOVI at: and for MEKTOVI at: 24

25 Global Colorectal Cancer Market Population Estimates CRC MUTATIONAL SUBGROUPS ANNUAL COLORECTAL CANCER MORTALITY 160, ,000 Annual CRC Mortality* 120, ,000 80,000 60,000 40,000 20,000 0 US EU Japan *Based on 2018 SEER and 2012 GLOBOCAN epidemiology reports 25

26 BEACON CRC Collaboration Array is the owner of binimetinib and encorafenib and will act as the global sponsor of the study. Pierre Fabre has elected to co-fund 40% of the cost of the BEACON CRC trial. Pierre Fabre licensed commercial rights to binimetinib and encorafenib for Europe and other global markets from Array in December Merck KGaA, Darmstadt, Germany, owns the rights to Erbitux outside the United States and Canada, and will supply Erbitux to all trial sites outside the United States and Canada as part of the collaboration. If successful, BEACON results would support regulatory submissions for all three parties. 26

27 STRATEGIC IMMUNO-ONCOLOGY PARTNERSHIPS & PORTFOLIO 27

28 MEK + PD-1/PD-L1 Development Strategy Collaborations advancing with Bristol-Myers Squibb, Merck & Pfizer Based on growing body of preclinical & clinical evidence that MEK inhibition may enhance the activity of immunotherapies, Array structured 3 clinical trial collaborations investigating the safety and activity of binimetinib with leading checkpoint inhibitors Binimetinib Combo Studies I/O partner Nivolumab (PD-1) Pembrolizumab (PD-1) Avelumab (PD-L1) Initial Patient Population RASm MSS colorectal cancer MSS colorectal cancer Pancreatic cancer & NSCLC Line Therapy 2 nd or 3 rd line 1 st or 2 nd line 2 nd or 3 rd line Trial Sponsor Array Merck Pfizer Triple Combination Option (+/-) Ipilimumab (CTLA-4) FOLFOX (Chemo) or FOLFIRI (Chemo) Talazoparib (PARP) 28

29 SECOMBIT/Sequential Combo Immuno and Targeted Therapy Trial ONE OF THE MOST COMPREHENSIVE STUDIES ASSESSING SEQUENCING STRATEGIES FOR TARGETED AND IMMUNOTHERAPIES IN BRAF-MUTANT MELANOMA Evaluate best sequencing approach with combination of targeted agents (binimetinib + encorafenib) and the combination of immunomodulatory antibodies (ipilimumab + nivolumab) in patients with BRAF-mutant melanoma Multicenter, international cooperative group trial sponsored by: Clinical Research Technology and Fondazione Melanoma Onlus; supported jointly by Bristol-Myers Squibb and Array (via Novartis) Patients with BRAF-Mutant Melanoma n=230 Randomization Binimetinib + Encorafenib Ipilimumab + Nivolumab Binimetinib + Encorafenib Progression Progression 2 Cycles Ipilimumab + Nivolumab Binimetinib + Encorafenib Progression Ipilimumab + Nivolumab Binimetinib + Encorafenib Primary Endpoint: Overall survival (OS) Key Secondary Endpoint: Progression free survival (PFS) 29

30 IMMU-TARGET in BRAF Melanoma Patients PD-1 + MEK + BRAF TRIPLE COMBINATION Investigate benefit of treating BRAF mutant melanoma patients with concurrent pembrolizumab (PD-1) + binimetinib (MEK) + encorafenib (BRAF) triple therapy Trial sponsor: Dr. Dirk Schadendorf, University Hospital, Essen, Germany Trial planned to enroll 140 patients Phase 1 Phase 2 Safety / Combinability of pembrolizumab + binimetinib + encorafenib Triple therapy (pembrolizumab + binimetinib + encorafenib) Defined 6 month course of therapy Randomization Triple therapy (pembrolizumab + binimetinib + encorafenib) Monotherapy (pembrolizumab) Primary Endpoint: Establish RP2D Primary Endpoint: Progression Free Survival (PFS) Secondary Endpoints: Safety, Overall Survival, Objective Response Rate 30

31 ARRY-382 (CSF-1R) + pembrolizumab (PD-1) Phase 1b/2 Trial Encouraging early signs of activity in tumors that have been historically unresponsive to anti-pd1 therapies RECOMMENDED PHASE 2 DOSE ARRY mg daily in combination with pembrolizumab 2 mg/kg given intravenously every 3 weeks PATIENTS AND TUMOR TYPES 19 patients, with a median of 2 prior lines of therapy and 42% with 3 prior regimens, were treated in the study. Patients with pancreatic (n=6), colorectal (n=5), ovarian (n=3), gastric and melanoma (n=2, each), and triple negative breast cancer (n=1) were enrolled CLINICAL ACTIVITY The combination demonstrated early signs of activity, with 2 partial responses reported: 1st responder, who was treated with ARRY-382 at 200 mg, had Stage III pancreatic ductal adenocarcinoma. As of the data cut-off, this patient was on study treatment in cycle 14 (42 weeks) Safety/Tolerability of ARRY-382 ARRY-382 had a manageable safety profile when administered with pembrolizumab in this study Most common grade 3/4 adverse events (AEs) (>10%), regardless of causality, included increased AST, increased blood CK, rash, increased lipase, increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT) and anemia 2nd responder, who was treated with ARRY-382 at 300 mg, had stage IV ovarian cancer with liver metastasis. As of the data cut-off, this patient was on study treatment in cycle 8 (24 weeks) 31

32 ARRY-382 (CSF-1R) Phase 1b/2 Trial Immuno-oncology trial in combination with pembrolizumab (PD-1) in solid tumors EXPANSIONS PHASE 1B DOSE ESCALATION ARRY pembrolizumab n = 19 patients with solid tumors Establish MTD/RP2D ARRY pembrolizumab in patients with pancreatic cancer with 1 prior line of therapy and no prior treatment with immune checkpoint inhibitors ARRY pembrolizumab in patients with solid tumors who have progressed on prior PD1/PD-L1 inhibitors ARRY pembrolizumab in patients with ovarian cancer who are platinum refractory and no prior treatment with immune checkpoint inhibitors Primary Endpoint: MTD/RP2D (Phase 1b); ORR (expansions) Secondary Endpoint: Safety, PK/PD and standard efficacy measures 32

33 AGREEMENTS WITH PIERRE FABRE & NOVARTIS 33

34 Strategic Collaboration with Pierre Fabre Oncology Benefits to Array $30 million upfront PIERRE FABRE IS A STRONG EUROPEAN COMMERCIAL PARTNER Europe is leading geographic priority with robust emerging market capability to provide scale to collaboration Significant footprint in Oncology Development, Sales & Marketing Willing to commit significant resources to ensure binimetinib and encorafenib success Providing robust downstream economics (royalties) for ready-to-file products The agreement was reviewed and approved by the European Commission on Competition in December % funding for certain future clinical development, including Phase 3 BEACON trial Up to $425 million in potential development and commercialization milestones Robust, tiered double-digit royalties Commercialization Rights Array retains exclusive rights in: United States Canada Israel May Ono Pharmaceuticals will have exclusive rights in Japan and South Korea Pierre Fabre will have exclusive rights in all other geographies, including Europe, Asia and Latin America 34

35 Novartis Agreement for Binimetinib & Encorafenib Transactions Closed on March 2, 2015 UNDER THE NOVARTIS AGREEMENT, ARRAY IS PROVIDED: $100 million+ net cash value Completion and/or substantial funding for all ongoing and several planned clinical trials Access to several Novartis pipeline agents for future combination trials including, but not limited to, LEE011 (CDK 4/6 inhibitor) and BYL719 (α-pi3k inhibitor) Continued clinical and commercial supply and support for technology transfer Conducting and fully funding the NRAS companion diagnostic program 35

36 Selected Encorafenib & Binimetinib Exploratory Trials Disease state Compound(s) Est. Patient Phase 1 Phase 1B Phase 2 Phase 3 BRAF V600+Melanoma Encorafenib + Binimetinib ± LEE011 (CDK 4/6) 179 BRAF V600+Melanoma Encorafenib + Binimetinib + Third Agent* 140 BRAF V600+Melanoma Binimetinib + Opdivo + Yervoy** 270 BRAF V600+Melanoma Encorafenib + Binimetinib + Keytruda** 140 BRAF V600+Melanoma Encorafenib + Binimetinib; Opdivo+Yervoy** 230 LOGIC2 EBIN IMMU-TARGET SECOMBIT BRAF+Metastatic Colorectal Cancer Encorafenib + Cetuximab ± BYL719 (PI3Kα) 150 MSS Colorectal Cancer Binimetinib + Opdivo ± Yervoy <100 MSS Colorectal Cancer Binimetinib + Keytruda 220 Colorectal Cancer Binimetinib + Xalkori** <100 KRAS Non-small cell lung cancer Binimetinib + Ibrance** <100 Triple Negative Breast Cancer Binimetinib + Keytruda** <100 NF1-associated Plexiform Neurofibromas Binimetinib** <100 Solid Tumors Binimetinib + BKM120 (Pan-PI3K) <100 Pediatric Low Grade Gliomas and CNS Tumors Binimetinib** 111 MErCuRIC Encorafenib + Binimetinib Encorafenib Binimetinib * Third agent: LEE011 (CDK 4/6 inhibitor), pan FGFR inhibitor, BKM120 (pan PI3K inhibitor) or c-met inhibitor; clinical pharmacology studies not listed above ** Investigator-sponsored trial (IST) The use of encorafenib and binimetinib in these diseases are investigational and have not been approved by the U.S. Food and Drug Administration. This information is presented only for purposes of providing a general overview of clinical trials. 36

37 ARRY-797 Phase 3 Trial Underway p38 Inhibitor for LMNA-Related DCM 37

38 ARRY-797 LMNA A/C-RELATED DCM A rare, degenerative cardiovascular disease caused by mutations in the LMNA gene and characterized by poor prognosis CLINICAL DEVELOPMENT Phase 3 trial of ARRY-797 underway Phase 2 results 1 Primary Endpoint: The absolute mean change from baseline was 69 meters on the six-minute walk test (6MWT) at week 12 (baseline 6MWT ranged from 246 to 412 meters) ARRY-797 was well tolerated with most patients experiencing mild to moderate adverse events, including stomatitis, acne and upper respiratory tract infection ARRY p38 Inhibitor for LMNA-Related Dilated Cardiomyopathy (DCM); 1 European Society of Cardiology Congress

39 LMNA-Related Dilated Cardiomyopathy (DCM) LMNA-RELATED DCM IS A RARE, DEGENERATIVE CARDIOVASCULAR DISEASE CHARACTERIZED BY DCM diagnosis (ejection fraction <40%, dilated ventricle) Presence of mutations in lamin A/C gene Poor prognosis, ~70% of patients have death, major cardiac event or transplant by age 45 1 By comparison, only 25% of DCM patients who do not have LMNA mutations experience similar events by age 45. Events defined as cardio vascular (CV) death, heart transplant or major cardiac event U.S. Prevalence Estimate Dilated Cardiomyopathy (DCM) ~250,000 patients Idiopathic DCM ,000 patients LMNA-DCM 6-10,000 patients Diagnosed <1,000 LMNA-RELATED DCM UNDER-DIAGNOSED DUE TO INFREQUENT GENETIC TESTING Presence of LMNA mutation does not currently change treatment practice Early/mid-stage patients: ACE inhibitors, beta blockers and diuretics Advanced patients: Pacemaker/defibrillator, heart transplant 1 M.R.G. Taylor, et al., J. Am. Coll. Cardiol. 2003;41; This compound and its uses are investigational and have not been approved by the U.S. Food and Drug Administration. 39

40 ARRY-797 Proof-of-Concept Trial LMNA-Related Dilated Cardiomyopathy (DCM) LMNA-Related DCM Patients n=12 ARRY-797 (100 mg) ARRY-797 (400 mg) Crossover from lower to higher dose allowed for inadequate response Primary Endpoints: Change from baseline in 6-minute walk test (12 weeks) Secondary Endpoints Measures of left and right ventricular function Ejection fraction (Imaging study directly measures cardiac function); fractional area shortening Circulating biomarkers of cardiac function N-Terminal pro-brain Derived Natriuretic Peptide: Blood test that indirectly measures cardiac wall stress and severity and prognosis in cardiac failure Disease specific patient reported outcomes: Measures patient perception of improvement in functional status Others Patients: Prior to enrollment, all patients were identified as having stable New York Heart Association class II IIIa congestive heart failure and eleven patients had an implantable cardioverter defibrillator. All patients were receiving multiple heart failure medications. Trial Sites: Brigham and Women s Hospital/Harvard, Johns Hopkins Univ., Meriter Wisconsin Heart, Univ. of Colorado, Ohio State Univ., Stanford Univ. *6MWT: Integrated assessment of cardiac, respiratory, circulatory, and muscular capacity that has served as a basis for regulatory approvals of a number of drugs across therapeutic areas including cardiovascular diseases. This compound and its uses are investigational and have not been approved by the U.S. Food and Drug Administration. 40

41 ARRY-797 Proof-of-Concept Trial Early & Sustained Improvements in 6 Minute Walk Test baseline 6MWT ranged from 246 to 412 meters 6MWT Change from BL, m Change from BL, % Wk 4 (n=12) Wk 12 (n=9) Wk 12* (n=12) Wk 24 (n=8) Wk 36 (n=8) Wk 48 (n=8) Wk 72 (n=4) Mean (SD) 47 (49) 69 (72) 71 (68) 54 (63) 63 (44) 55 (52) 59 (57) Median Mean (SD) 15 (18) 17 (23) 23 (23) 18 (23) 21 (16) 19 (19) 19 (18) Median MWT=6-minute walk test; BL=baseline. *Includes imputed data from 3 patients not completing the week 12 visit; the last-observation-carried-forward method was employed. ARRY-797 administration also resulted in sustained improvements in NTproBNP, functional capacity and cardiac function through 48 weeks Patients who rolled over to a continuing treatment protocol maintained improvements in the 6MWT and NT-proBNP levels through 72 weeks of treatment. Other secondary endpoints measured including echocardiographic measures of left and right ventricular function and patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ), both mirrored the favorable improvements seen with the 6MWT. Presented at ESC, August 30, 2016 (Abstract P4981) This compound and its uses are investigational and have not been approved by the U.S. Food and Drug Administration. 41

42 ARRY-797 Proof-of-Concept Trial Tolerability Profile ARRY-797 was well tolerated, with most patients experiencing mild to moderate adverse events, including stomatitis, acne and upper respiratory tract infection. None of the grade 3 / 4 adverse events were considered to be related to ARRY-797 by the investigators. Four patients discontinued the study. One patient discontinued due to availability of a heart for transplant, two patients for interventional cardiovascular procedures and one patient due to grade 2 stomatitis. Presented at ESC, August 30, 2016 (Abstract P4981) This compound and its uses are investigational and have not been approved by the U.S. Food and Drug Administration. 42

43 Historical Benchmarks for 6 Minute Walk Test Product Company Indication FDA Approved 6MWT: Mean Change vs. Baseline (Absolute Meters) Bosentan Actelion PAH Yes Idursulfase Shire MPS II Yes Riociguat Elosulfase Alfa Bayer CTEPH & PAH Yes BioMarin MPS IVA Yes Ambrisentan Gilead PAH Yes Laronidase Genzyme MPS I Yes Meters 43

44 SELUMETINIB IN CANCER & NF1 Registration Trial 44

45 Selumetinib (AstraZeneca) NF1 Registration Study Underway Key Deal Terms Potential Royalty: Double-digits Potential Milestones Remaining: $30 million specific for selumetinib Structure: AstraZeneca responsible for global development and commercialization Registration Trial Neurofibromatosis Type 1 (100,000 individuals in U.S.) Single agent; confirmed response rate by volumetric MRI; n=50 ENROLLING 45

46 No Standard Medical Therapies for Patients with NF1/PN Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that can cause tumors to grow on nerves throughout the body 1 Most tumors are inoperable NF1 may lead to blindness, bone abnormalities, cancer, deafness, disfigurement, learning disabilities and excruciating and disabling pain NF affects one in every 3,000 individuals NF affects more than cystic fibrosis, Duchenne muscular dystrophy and Huntington s disease combined 3 Years 5 Years PN Limits Mobility of Left Arm 1 C. Widemann, M.D., N Engl J Med 2016; 375: This compound and its uses are investigational and have not been approved by the U.S. Food and Drug Administration. 46

47 Selumetinib in NF1 Pediatric Patients Objective Responses Seen in 71% of Patients 1 Partial Response (PR)* 71% (17 out of 24) Progressive Disease (PD)* 0% Common Adverse Events (AEs) Acneiform rash, asymptomatic CK elevation, GI Median Cycle (1 Cycle = 28 Days) 30 (6-56) Durability Anecdotal Observations 15 of the 17 patients with partial response maintain their response status to date (last patient recruited Feb. 2014) Decreases in tumor-related pain, disfigurement & functional impairment *PR and PD Defined by NCI investigators as a PN volumetric decrease of 20% using MRI This compound and its uses are investigational and have not been approved by the U.S. Food and Drug Administration. Patient 20: the visible reduction PN burden is depicted in the MRI results and photographs before treatment as compared with those at the end of cycles 5 and 10 during treatment. 1 C. Widemann, M.D., N Engl J Med 2016; 375:

48 Financials 48

49 Fourth Quarter and Full Year of Fiscal 2018 Financial Results 49

50 Appendix 50

51 BRAFTOVI capsules in combination with MEKTOVI tablets Important Safety Information Warnings and Precautions New Primary Malignancies: New primary malignancies, cutaneous and non-cutaneous malignancies can occur. In the COLUMBUS trial, cutaneous squamous cell carcinoma, including keratoacanthoma, occurred in 2.6% and basal cell carcinoma occurred in 1.6% of patients. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies. Tumor Promotion in BRAF Wild-Type Tumors: Confirm evidence of BRAF V600E or BRAF V600K mutation prior to initiating BRAFTOVI. Cardiomyopathy: In the COLUMBUS trial, cardiomyopathy occurred in 7% and Grade 3 left ventricular dysfunction occurred in 1.6% of patients. Cardiomyopathy resolved in 87% of patients. Assess left ventricular ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. The safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal. Venous Thromboembolism (VTE): In the COLUMBUS trial, VTE occurred in 6% of patients, including 3.1% of patients who developed pulmonary embolism. Hemorrhage: In the COLUMBUS trial, hemorrhage occurred in 19% of patients and Grade 3 hemorrhage occurred in 3.2% of patients. Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients. Ocular Toxicities: In the COLUMBUS trial, serous retinopathy occurred in 20% of patients; 8% were retinal detachment and 6% were macular edema. Symptomatic serous retinopathy occurred in 8% of patients with no cases of blindness. In patients with BRAF mutation-positive melanoma across multiple clinical trials, 0.1% of patients experienced retinal vein occlusion (RVO). Permanently discontinue MEKTOVI in patients with documented RVO. In COLUMBUS, uveitis, including iritis and iridocyclitis, was reported in 4% of patients. Assess for visual symptoms at each visit. Perform ophthalmic evaluation at regular intervals and for any visual disturbances. Interstitial Lung Disease (ILD): ILD, including pneumonitis, occurred in 0.3% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD. 51

52 BRAFTOVI capsules in combination with MEKTOVI tablets Important Safety Information Hepatotoxicity: In the COLUMBUS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 6% for alanine aminotransferase (ALT) and 2.6% for aspartate aminotransferase (AST). Monitor liver laboratory tests before and during treatment and as clinically indicated. Rhabdomyolysis: In the COLUMBUS trial, elevation of laboratory values of serum creatine phosphokinase (CPK) occurred in 58% of patients. Rhabdomyolysis was reported in 0.1% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Monitor CPK periodically and as clinically indicated. QTc Prolongation: In the COLUMBUS trial, an increase in QTcF to >500 ms was measured in 0.5% (1/192) of patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms. Embryo-Fetal Toxicity: BRAFTOVI or MEKTOVI can cause fetal harm when administered to pregnant women. Nonhormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI + MEKTOVI. Adverse Reactions The most common adverse reactions ( 20%, all Grades, in the COLUMBUS trial) were: fatigue, nausea, diarrhea, vomiting, abdominal pain, arthralgia, myopathy, hyperkeratosis, rash, headache, constipation, visual impairment, serous retinopathy. In the COLUMBUS Trial, the most common laboratory abnormalities ( 20%, all Grades) included: increased creatinine, increased CPK, increased gamma glutamyl transferase, anemia, increased ALT, hyperglycemia, increased AST, and increased alkaline phosphatase. Drug interactions Avoid concomitant use of strong or moderate CYP3A4 inhibitors or inducers and sensitive CYP3A4 substrates with BRAFTOVI. Modify BRAFTOVI dose if concomitant use of strong or moderate CYP3A4 inhibitors cannot be avoided. 52

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