Array BioPharma COLUMBUS: Met Primary Endpoint. September 26, 2016

Transcription

1 Array BioPharma COLUMBUS: Met Primary Endpoint September 26, 2016

2 Safe Harbor Statement 2 This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements about the future development plans of binimetinib and encorafenib, and the timing of the announcement of further results of clinical trials for binimetinib and encorafenib; expectations regarding the timing of regulatory filings for binimetinib and encorafenib and regarding approval of binimetinib and encorafenib for BRAF-mutant melanoma; expectations that events will occur that will result in greater value for Array; and the potential for the results of current and further clinical trials to support regulatory approval or the marketing success of binimetinib and encorafenib. Specifically, there is no assurance that results from the COLUMBUS study, including Parts 1 and 2, will satisfy the requirements of regulatory authorities necessary to file an application for marketing approval, or that if such application is accepted, that it will be approved. These statements involve significant risks and uncertainties, including those discussed in our most recent annual report filed on Form 10-K, in our quarterly reports filed on Form 10-Q, and in other reports filed by Array with the Securities and Exchange Commission. Because these statements reflect our current expectations concerning future events, our actual results could differ materially from those anticipated in these forward-looking statements as a result of many factors. These factors include, but are not limited to, the determination by the FDA that results from clinical trials are not sufficient to support registration or marketing approval of binimetinib and encorafenib; our ability to effectively and timely conduct clinical trials in light of increasing costs and difficulties in locating appropriate trial sites and in enrolling patients who meet the criteria for certain clinical trials; risks associated with our dependence on third-party service providers to successfully conduct clinical trials within and outside the United States; our ability to achieve and maintain profitability and maintain sufficient cash resources; and our ability to attract and retain experienced scientists and management. We are providing this information as of September 26, We undertake no duty to update any forward-looking statements to reflect the occurrence of events or circumstances after the date of such statements or of anticipated or unanticipated events that alter any assumptions underlying such statements.

3 COLUMBUS Trial Met Primary Endpoint 3 Primary Endpoint Part 1 combination of encorafenib plus binimetinib ( combination ) demonstrated robust statistically significant improvement in PFS when compared to vemurafenib: mpfs 14.9 months vs. 7.3 months, HR (0.54), [95% CI, ], p<0.001 Combination was generally well tolerated and demonstrated a safety profile overall consistent with previously published encorafenib plus binimetinib clinical trial results in patients with BRAF-mutant melanoma Additional results from trial, including objective response rate, duration of response, detailed safety, exploratory analyses such as a Part 1 PFS comparison of encorafenib to vemurafenib and pre-specified subgroup analyses (including patients who received prior immunotherapy) will be presented at an upcoming medical conference Global regulatory submissions are planned for 2017

4 COLUMBUS Trial Update 4 Analysis of a secondary endpoint comparing the PFS of patients treated with the combination to patients treated with encorafenib showed a median of 14.9 months versus 9.6 months with HR (0.75), [95% CI ], p=0.051 which was not statistically significant - A complete analysis of these results will be provided to global regulatory authorities as part of planned submissions Data from Part 2 of the COLUMBUS trial are anticipated in mid 2017 and will also be provided to global health authorities as part of planned regulatory submissions for approval of these product candidates Analysis of Overall Survival was not planned or performed as part of these initial results Array BioPharma retains exclusive rights to binimetinib and encorafenib in key markets including U.S. & Japan

5 COLUMBUS Trial Design 5 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 Arm A Binimetinib (45 mg) + Encorafenib (450mg) Arm B Vemurafenib Arm C Encorafenib (300mg) Arm D Binimetinib (45 mg)+ Encorafenib (300mg) Arm C Encorafenib (300mg) Primary Endpoint: Progression Free Survival (PFS) comparison of Arm A vs. Arm B Secondary Endpoints: PFS Arm A vs. Arm C, PFS Part 2, Overall Survival, Objective Response Rate, Safety Endpoints, QoL

6 Global Melanoma Market Population Estimates for Advanced/Metastatic Melanoma Patients 6 Melanoma Mutational Subgroups NEMO population NRASm ~20% BRAF/NR AS WT ~30% BRAFm ~50% Annual Melanoma Mortality* Estimated Annual Incidence Advanced/Metastatic Melanoma Patients 20,000 18,000 16,000 14,000 12,000 10,000 8,000 6,000 4,000 COLUMBUS population 2,000 0 US EU Japan * Based on SEER and GLOBOCAN epidemiology reports

7 Global Melanoma Market Annual Sales of Approved MEK/BRAF Inhibitors Approaching $1 Billion 7 $250 $200 $150 $100 $50 $0 Quarterly Sales of Approved MEK + BRAF inhibitors* Cotellic FDA approved Q Q Q Q Q Q Quarterly global sales nearly $250 million while annual US sales approaching$40 0 million Binimetinib and Encorafenib are Unapproved, Investigational Drugs Novartis Products US WAC (Month)** Roche Products US WAC (Month)** Mekinist $10,387 Zelboraf $10,971 Tafinlar $9,475 Cotellic $6,567 Combo: $19,861 Combo: $17,538 * Novartis and Roche Quarterly Reports ** Red Book Sept 2016; does not include discounts/rebates

8 Binimetinib NDA Accepted For Review NRAS-mutant Melanoma

9 Binimetinib Phase 3 NEMO Study Results NDA Accepted for Review: June 30, 2017 PDUFA Date 9 Progression Free Survival (PFS) Confirmed Overall Response Rate (ORR) Disease Control Rate (DCR) Overall Survival (OS) Binimetinib n=269 Dacarbazine (DTIC) n= (95% CI, , p value < 0.001) % (95% CI, 11-20%) 58% (95% CI, 52-64%) 7% (95% CI, 3-13%) 25% (95% CI, 18-33%) 11.0 [(HR) = 1.0 (95% CI 0.75;1.33), p=0.499] 10.1 NEMO study met its primary endpoint of improving PFS compared with dacarbazine treatment Median PFS on the binimetinib arm 2.8 months versus 1.5 months on the dacarbazine arm [hazard ratio (HR)=0.62 (95% CI ), p<0.001] While the results in the prior immunotherapy subgroup are of interest, interpretation beyond overall consistency with the primary result should be made with care. Array anticipates that the primary consideration for marketing approval will be the primary endpoint results Pre-Specified Sub-Group of Patients Who Received Prior Immunotherapy (N=85) PFS About NRAS-Mutant Melanoma 5.5 (95% CI, ) 1.6 Binimetinib appeared to be generally well-tolerated Grade 3/4 AEs reported in 5% of patients receiving binimetinib included increased creatine phosphokinase (CPK) & hypertension NRAS mutations are present in up to 20% of patients with metastatic melanoma; treatment options for this population remain limited beyond immunotherapy, and patients face poor clinical outcomes and high mortality

10 Phase 3 BEACON CRC

11 Encorafenib + Binimetinib ± Cetuximab Phase 3 BRAF-Mutant Colorectal Cancer Study Design 11 SAFETY LEAD-IN 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 1-2 prior regimens in metastatic setting n=615 Randomization Arm A - Triplet Therapy Binimetinib + Encorafenib + Cetuximab n=205 Arm B - Doublet Therapy Encorafenib + Cetuximab n=205 Arm C - 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 will be conducted at over 250 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed in 2018.

12 Encorafenib Phase 2 BRAF-Mutant mcrc Encouraging Clinical Activity & Good Tolerability 12 Encorafenib + Cetuximab n=50 Encorafenib + Alpelisib (PI3K) + Cetuximab (EGFR) n=52 Overall Survival (OS) 12.4 mos mos. Progression Free Survival (PFS) Confirmed Overall Response Rate (ORR) 4.2 mos. (95% CI, ) 22% (95% CI, 12-36%) All Cause Adverse Events (>32% in either treatment group) 5.4 mos. (95% CI, ) 27% (95% CI, 16-41%) Diarrhea 28% 54% Nausea 46% 54% Vomiting 32% 50% Fatigue 50% 46% Abdominal Pain 42% 38% Decreased Appetite 34% 37% Historical Published Results after First-Line Treatment OS results range between 4 to 6 months PFS range between 1.8 to 2.5 months ORR range between 6% to 8% About CRC CRC is 3 rd most common cancer in the U.S., with approximately 134,000 new cases and nearly 50,000 deaths from the disease projected in 2016 In the U.S., BRAF mutations occur in 10 to 15% percent of patients with CRC and predict for a poor response to standard therapies and an overall poorer prognosis relative to patients without these mutations Weight Decrease 34% 37% Hyperglycemia 10% 37% Rash 16% 33% Arthralgia 34% 27% Phase 2 trial Includes BRAF-mutant CRC patients who have progressed after one or more prior therapies

13 Observed Overall Survival from Phase 2 Greater Than Historical Controls 13 Median OS in 2 nd Line+ BRAFm mcrc Studies Median OS in Months Informed the initiation of Phase 3 BEACON CRC encorafenib + cetuximab 6 2 nd Line+ n = 50 encorafenib + cetuximab+ alpelsib 6 2 nd Line+ n = 52 cetuximab + chemo 1 2 nd Line+ n = 24 cetuximab + chemo 2 2 nd Line+ n = 12 FOLFIRI 3 2 nd Line n = 23 FOLFIRI + panitumamab 3 2 nd Line n = 22 cetuximab + chemo 4 2 nd Line+ n = 22 cetuximab + irinotecan 5 2 nd Line+ n = 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 Tabernero et al., ASCO 2016

14 Global Colorectal Cancer Market Population Estimates 14 CRC Mutational Subgroups Annual Colorectal Cancer Mortality BEACON CRC population BRAFm ~10-15% BRAF WT ~85-90% Annual CRC Mortality* 160, , , ,000 80,000 60,000 40,000 20,000 0 US EU Japan * Based on SEER and GLOBOCAN epidemiology reports

15 Additional Value Drivers

16 Additional Drivers of Potential Value for Array BioPharma 16 - Encouraging results from a Phase 2 study of ARRY-797 in patients with LMNA A/Crelated dilated cardiomyopathy were presented at European Society Cardiology in August Magnitude of improvement on 6-minute walk test (absolute mean improvement of 69 meters at 12 weeks) exceeded historical benchmarks that served as the basis for recent approvals of other drugs in other rare diseases. - Novel immuno-theraputic ARRY-382 (CSF1R inhibitor) initiated Phase 1/2 trial in combination with Keytruda - Acceptable combinability will lead to expansions in advanced melanoma and/or non small cell lung cancer patients - Array pursuing Japan/Korea partnership for encorafenib and binimetinib

17 Thank You arraybiopharma.com