Developing & Commercializing Targeted Small Molecule Drugs in Cancer

Transcription

1 Developing & Commercializing Targeted Small Molecule Drugs in Cancer Jefferies 2015 Global Healthcare Conference Ron Squarer, Chief Executive Officer June 2, 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, 2014, 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 Path to Commercialization Upcoming Catalysts for Binimetinib & Encorafenib European Partner Selection Expected in 2015 Initial regulatory submissions are expected in 2016 for both products 1H H H H 2016 PROJECTED REGULATORY FILINGS PHASE 3 ENROLLMENT AND RESULTS NEMO LPFV COLUMBUS Part 1 LPFV NEMO Top-Line Results COLUMBUS Part 1 Top-Line Results MILO Top-Line Results PHASE 1 / 2 DATA AVAILABILITY ASCO 2015 Ph 1/2 BRAF Melanoma Ph 1/2 GIST w/imatinib Ph 1/2 NRAS melanoma w/lee011 Ph 1/2 BRAF melanoma LOGIC-2 Ph 1/2 BRAF CRC w/cetuximab Planned publications for 2016 TBD 3

4 Binimetinib & Encorafenib Clinical Data Presentations Type Phase Indication Title Binimetinib and/or Encorafenib ORAL Phase 1b/2 BRAF-mutant melanoma A phase 1b/2 study of BRAF inhibitor (BRAFi) encorafenib (ENCO) plus MEK inhibitor (MEKi) binimetinib (BINI) in cutaneous melanoma patients naive to BRAFi treatment ORAL Phase 1b/2 Gastrointestinal stromal tumor A phase Ib/II study of MEK162 (binimetinib [BINI]) in combination with imatinib in patients with advanced gastrointestinal stromal tumor Poster Phase 1b Epithelial ovarian, fallopian tube or primary peritoneal cancer A phase 1b dose-escalation study of binimetinib (MEK162) in combination with weekly paclitaxel in patients with platinumresistant epithelial ovarian, fallopian tube or primary peritoneal cancer Publication Phase 1 Biliary cancer A phase I trial of MEK162 in combination with gemcitabine (G) and cisplatin (C) patients (pts) with untreated advanced biliary cancer Binimetinib and encorafenib was also featured in other preclinical or trials in progress presentations. 4

5 Previously Published MEK/BRAF Safety Profile & Clinical Activity Trametinib + dabrafenib 1 Novartis COMBI-D (n=210) Trametinib + dabrafenib 2 Novartis COMBI-V (n=352) Cobimetinib + vemurafenib 3 Roche - cobrim (n=247) Fever 51% 53% 26% Rash 23% 22% 39% SELECT ADVERSE EVENTS OF INTEREST Diarrhea Chills 24% 32% 30% 31% 57% NR (<20%) Hypertension 22% 26% NR (<20%) Photosensitivity NR (<10%) 4% 28% NR = Not Reported COMBI-D (n=210) COMBI-V (n=352) cobrim (n=247) ORR (CR + PR) BRAFi naive 67% 64% 68% 5 1 Long et al N Engl J Med. 2014; 2 ESMO 2014; 3 Larkin et al N Engl J Med. 2014

6 ASCO 2015 Oral Presentation: Ph1/2 LGX + MEK in BRAF mut melanoma/brafi-naïve pts ASCO 2015 POSTER Phase 1b/2 Dose Escalation BRAFi naïve, BRAF-mutant melanoma Demonstrated Preliminary Clinical Activity in BRAFm Melanoma Binimetinib 45mg BID / Encorafenib 400/450mg QD (n=9) Partial response (PR) 67% (6 of 9) Complete response (CR) 11% (1 of 9 Stable disease (SD) 22% (2 of 9) Objective Response Rate (ORR) 78% Differentiated Safety Profile 11% pyrexia, photosensitivity; few gr 3/4 events reported Overall Study Population (n=55) Partial response (PR) 62% (34 of 55) Complete response (CR) 13% (7 of 55) Stable disease (SD) 22% (12 of 55) 6 Median Progression Free Survival 11.3 months

7 Binimetinib+Encorafenib+Third Agent - LOGIC-2 BRAF Melanoma Data Expected in 2015 Patient enrollment on-going N=140 PART 1 PART 2 Group A BRAF & MEK naïve patients Group A Binimetinib + Encorafenib Group A Binimetinib + Encorafenib+third agent Group B Patients with any BRAF/MEK combo or single agents (non-naïve) Group B Run-in Binimetinib + Encorafenib After progressive disease, genetic assessment performed to determine combination Group B Binimetinib + Encorafenib+third agent Group C Patients prev. in Columbus, LOGIC1, CMEK162X2110, or Group A (non-naive) Group C Optional Binimetinib + Encorafenib Group C Binimetinib + Encorafenib+third agent Primary endpoint: Overall Response Rate (Part 2) Secondary endpoint: Safety 7 After PD in Part 1: Tumor biopsy genetic assessment performed to determine combination treatment in Part 2 Part 2 Third agent: LEE011 (CDK 4/6 inhibitor), BGJ398 (pan FGFR inhibitor), BKM120 (pan PI3K inhibitor) or INC280 (c-met inhibitor)

8 Binimetinib & Encorafenib Three Phase 3 Studies Underway FIRST INDICATION ADDITIONAL PIVOTAL TRIALS NEMO / NRAS-mutant Melanoma (20% of mel) PFS; n=393; 2:1 randomized binimetinib vs. DTIC; projected regulatory filing first half of 2016 COLUMBUS / BRAF-mutant Melanoma (40% of mel) PFS; n=900 Part 1: 1:1:1 randomized with 1) Encorafenib (450mg) plus binimetinib 2) Encorafenib (300mg) as monotherapy 3) Vemurafenib projected regulatory filing 2016 Part 2: 3:1 randomization with 1) Encorafenib (300mg) plus binimetinib 2) Encorafenib (300mg) as monotherapy ENROLLMENT COMPLETE ENROLLMENT COMPLETE Part 1 ENROLLING TOTAL TRIALS MILO / Low-Grade Serous Ovarian Cancer PFS; n=360; 2:1 randomized binimetinib vs. physicians choice chemo (crossover permitted); projected regulatory filing active trials ENROLLING 8

9 Phase 2 - Binimetinib in Advanced NRAS Melanoma Median Overall Survival (mos) Encouraging 117 NRAS+ melanoma patients 12.2 months mos Historical published prognosis for NRAS+ melanoma patients is 8.2 months a 3.6 months mpfs Confirms interim results reported at ASCO % confirmed objective response rate (CR+PR) & 56.4% disease control rate ( SD) b Adverse events were generally mild to moderate in severity, and frequency and severity were similar to what has been previously reported Most common AE: dermatitis acneiform, increased blood creatine phosphokinase and peripheral edema, consistent with previous MEK-inhibitor class effects No treatment-related deaths were reported in this population 9 a NRAS Mutation Status is an Independent Prognostic Factor in Metastatic Melanoma, Cancer August 15; 118(16): b In six patients, post-baseline assessment was missing. In four patients, metastases (bone, brain or both) were not followed up. For each of the remaining two patients, postbaseline scan showed stable disease; however, the post-baseline CT scan was taken before 6 weeks following the first dose (not performed as per RECIST guidelines).

10 Mutation Prevalence MEK & BRAF Opportunities Ras/Raf/MEK/Erk pathway mutations implicated in multiple cancer indications Encorafenib and/or Binimetinib Pivotal Trials Underway in Selected Cancer Populations Mutation Other (NF1, SPRED, SOS1) GNAQ/GNA NSCLC (322,000) 1 Thyroid (231,000) Ovarian (43,000) Melanoma Ocular Colorectal Pancreatic (30,000) Melanoma (213,000) (65,000) (11,000) 3 2 BRAF NRAS KRAS 10 Indication (US Prevalence) Data Source: Sanger Institute COSMIC Database (Nov 6, 2012) 1 Mascaux C et al. Br J Cancer 2005;92: Eser S et al. Br J Cancer 2014;111: Majority of thyroid patients treated with surgery & radioactive iodine

11 Ph. 1 BRAF-mut. mcrc Nov EORTC-NCI-AACR Promising Antitumor Activity & Acceptable Safety Ph. 1 arm = 54 patients (current data) Ph. 2 arm = 100 patients (enrolling) 11

12 Ph. 1 BRAF-mut. mcrc April 2015 AACR Annual Meeting Phase 1, Dual Combination Arm (encorafenib + cetuximab) 31% of patients received treatment benefit for more than 1 year Complete response (CR) Partial response (PR) Stable disease (SD) Progressive disease (PD) Unknown Ongoing Duration of exposure, weeks Data cutoff date: February 1, 2015.

13 Selected Binimetinib & Encorafenib Exploratory Trials INDICATION DRUG(S) EST. PATIENT PHASE 1 PHASE 1B PHASE 2 PHASE 3 BRAF V600+ melanoma Bini + Encor ± LEE011 (CDK 4/6) 179 Selected tumors Bini and Encor as single agents <100 BRAF V600+ melanoma Bini + Encor plus third agent* 140 BRAF+ mcrc Encor + Cetuximab ± BYL719 (PI3Kα) 150 LOGIC-2 BRAF+ mcrc Encor + Cetux. + WNT974 <100 BRAF V600+ melanoma Encor + LEE011 (CDK 4/6) <100 BRAF V600+ tumors Encorafenib single agent <100 RAS or BRAF+ solid tumors Binimetinib + BYL719 (PI3Kα) <100 NRAS melanoma Binimetinib + LEE011 (CDK 4/6) <100 Mutant or wild-type RAS mcrc Binimetinib + Panitumumab <100 Uveal Melanoma Binimetinib + Protein kin. C <100 Solid tumors Binimetinib + Ganitumab <100 Ovarian cancer Binimetinib + Paclitaxel <100 Solid tumors Bini + BKM120 (pan-pi3k) <100 Binimetinib + Encorafenib Encorafenib Binimetinib 13 *Third agent: LEE011 (CDK 4/6 inhibitor), pan FGFR inhibitor, BKM120 (pan PI3K inhibitor) or c-met inhibitor Investigator-sponsored trials and clinical pharmacology studies not listed above

14 Encorafenib & Binimetinib Status Update Transactions closed on March 2, active binimetinib and/or encorafenib clinical trials including three Phase 3 trials, with regulatory filings planned in 2016 Under the Novartis agreement, Array is provided: $85 million milestone plus reimbursement for certain transaction-related expenses Elimination of $21.6 million payment obligation 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 BRAF and NRAS companion diagnositc program Array is in discussions to identify an appropriate partner for global development & European commercialization 14

15 Selumetinib (AstraZeneca) Phase 3 Studies Underway KEY DEAL TERMS FIRST INDICATION Potential Royalty: Double-digits Potential Milestones Remaining: $70M Structure: AZ responsible for global development & commercialization SUMIT / Uveal Melanoma with dacarbazine; PFS; n=128; 1:1 randomization vs. dacarbazine plus placebo; projected regulatory filing 2015 ENROLLMENT COMPLETE ADDITIONAL PHASE 3 TRIALS SELECT-1 / KRAS-mutant NSCLC (20-25% of NSCLC) with docetaxel; PFS; n=634; 1:1 randomization vs. docetaxel plus placebo; projected regulatory filing 2017 ENROLLING CYTOTOXIC COMBINABILITY ASTRA / Thyroid Cancer with RAI; Complete remission rate; n=304, 1:1 randomized vs. placebo; projected regulatory filing 2017 Selumetinib combines successfully with docetaxel & other chemo at MTD ENROLLING 15

16 Selumetinib Development Pipeline Selected Trials Phase 3 Studies Underway INDICATION COMBINATION DRUG EST. PATIENT PHASE 1 PHASE 1B PHASE 2 PHASE 3 KRAS NSCLC Docetaxel 634 Uveal Melanoma Dacarbazine 128 Thyroid Cancer Radioactive Iodine Therapy 304 Unselected 2 nd -line+ NSCLC Erlotinib, MK-2206, sorafenib 450 KRAS/NRAS/HRAS/BRAF NSCLC MK-2206, lapatinib, erlotinib, sunitinib 600 SELECT-1 SUMIT ASTRA BATTLE-2 NSCLC Selumetinib,AZD2014, AZD4547, AZD5363, AZD8931, vandetanib, erlotinib or pemetrexed 650 KRAS Wildtype or Unknown Non-Squamous NSCLC Pemetrexed, cisplatin 140 Unselected 1 st -line NSCLC Gemcitabine and cisplatin <100 Unselected 1 st -line NSCLC (KRAS sub-analysis) Paclitaxel, carboplatin, pemetrexed, cisplatin <100 Unselected 2 nd -line+ NSCLC (Japan) Docetaxel <100 EGFR Advanced NSCLC AZD9291+selumetinib, AZD9291+MEDI4736, or AZD9291+AZD TATTON Advanced NSCLC MEDI4736+selumetinib+docetaxel MEDI4736+gefitinib MEDI4736+AZD9291 MEDI4736+tremelimumab <100 Pancreatic Cancer MK2206 or FOLFOX 133 Neurofibromatosis - adults Single Agent <100 Registration studies Broad effort in NSCLC 16 Neurofibromatosis - peds Single Agent <100

17 ARRY-797 / p38 Inhibitor for LMNA-related DCM

18 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, including 31% event-free survival rate at age 45 1 Events defined as CV death, heart transplant or major cardiac event U.S. Prevalence Estimate Dilated Cardiomyopathy (DCM) ~250,000 patients Idiopathic DCM ,000 patients LMNA-DCM 6-8,000 patients <1,000 pts Diagnosed 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

19 Rationale for ARRY-797 in Treatment of LMNA Gene Mutation-Related DCM Mechanical stress-induced apoptosis has been proposed as the mechanism underpinning DCM in lamin A/C deficient hearts RAC1 Stress CDC42 Extracellular Cytoplasm p38 MAPK signaling regulates myocyte growth and survival in response to mechanical stress and has been implicated in cardiac dysfunction in laminopathies ARRY-797 is a potent inhibitor of p38 MAPK ARRY-797 normalizes left ventricular morphology and improves function in a LMNA N195K model of DCM Physician-sponsored single-patient IND indicated that ARRY-797 treatment has been associated with cardiac function improvements and was well tolerated 19 ARRY-797: p38 Inhibitor Nuclear Envelope p53 MAPKAP-K2 and K3 Transcription factors DNA Transcription / Translation ATF2 Fax MLK1 MKK3, 6 p38 MAPK p38 MAPK RNA binding proteins LMNA Genetic Mutation MEF2 Bax Apoptotic/survival pathways and cardiomyocyte remodeling factors Stress

20 ARRY-797 Phase 2 Trial Update Trial ongoing at 6 academic sites with a strong interest in DCM Patient experience out to 48 weeks Well-tolerated Preliminary data reviewed across patients are encouraging for multiple endpoints Further data needed to fully assess magnitude, consistency and durability of effects 20

21 Value Drivers

22 Array Expected Product Portfolio Value Drivers BINIMETINIB BINIMETINIB & ENCORAFENIB SELUMETINIB DRUG INDICATION(S) STATUS Binimetinib (MEK162) Binimetinib (MEK162) Encorafenib (LGX818) Selumetinib (AZD6244) (AstraZeneca) NRAS Melanoma LGS Ovarian Cancer BRAF Melanoma PH 3 NSCLC Thyroid Cancer Uveal Melanoma PH 3 PH 3 Q1 Q2 Q3 Q4 NEMO enrolled Phase 3 NEMO top-line results Phase 3 MILO enrollment ongoing COLUMBUS Part 1 enrolled Phase 3 COLUMBUS - Part 2 enrolling BRAF-mel. & GIST data/asco TATTON NSCLC data / ASCO Phase 3 SUMIT top-line results* Phase 3 SUMIT projected regulatory filing* NF-1 data later in 2015* NRAS, BRAF-mel. & CRC data Phase 3 SELECT-1 and ASTRA enrollment ongoing FILANESIB Filanesib (ARRY-520) Multiple Myeloma PH 2 Generating data from single-agent & Kyprolis-combo Phase 2 trials ARRY-797 ARRY-797 LMNA-related DCM PH 2 Additional results *Based on projections from AstraZeneca 22 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