Developing & Commercializing Targeted Small Molecule Drugs in Cancer

Transcription

1 Developing & Commercializing Targeted Small Molecule Drugs in Cancer Jefferies Global Healthcare Conference Ron Squarer, Chief Executive Officer June 4, 2014

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, 2013, 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 Array Value Proposition BINIMETINIB 3 Phase 3 studies underway, 17 trials on-going or planned in a range of cancers; Projected 2015 regulatory filing in NRAS melanoma (NEMO); ASCO 2014 data Co-development and option to co-detail approved products in U.S. with Novartis FILANESIB Novartis & GSK recently announced that they have entered into a definitive agreement to exchange certain assets Novel KSP inhibitor in development for multiple myeloma Wholly-owned Entering Phase 3 trials in 2014 ADDITIONAL NEAR TERM CATALYSTS Received orphan drug designation in May 2014 Selumetinib / MEK inhibitor now enrolling uveal melanoma pivotal study (projected 2015 regulatory filing) in addition to KRAS NSCLC & thyroid cancer. AZ announced near term Phase 3 first line KRAS NSCLC investment decision. ASCO 2014 data ARRY-797 / p38 inhibitor beginning Phase 2 studies in rare genetic CV disease preliminary results expected end of 2014; received orphan drug designation in May 2014 ARRY-614 / p38/tie2 inhibitor data maturing, regulatory discussions in 2014 ARRY-380 / HER2 inhibitor advancing in three metastatic breast cancer POC trials LOXO-101 / pantrk inhibitor now enrolling in Phase 1 3

4 Binimetinib Continues to Advance in the Clinic Three Phase 3 Trials BRAF & NRAS Mel, LGSOC 4 Novartis & GSK recently announced that they have entered into a definitive agreement to exchange certain assets, which includes GSK s commercial-stage MEK inhibitor Novartis has indicated that it will continue to honor its obligations under the Array-Novartis agreement, including obligations relating to support for ongoing clinical trials If Novartis binimetinib development & commercialization rights are returned to Array, Novartis must provide support for ongoing clinical studies as specified in our agreement Three Phase 3 trials with binimetinib continue to enroll: NRAS-mutant melanoma, low-grade serous ovarian cancer & BRAF-mutant melanoma NRAS-mutant melanoma represents the first potential indication for binimetinib, with a projected regulatory filing from the NRAS-mutant melanoma study estimated to be in 2015

5 Investigational Compounds Binimetinib + Novartis LEE011 (CDK4/6) in NRAS Melanoma ASCO 2014 ORAL PRESENTATION Phase 1b/2 (NCT ) NRAS Melanoma (N=22, as of 3/21/14) Demonstrated Promising Preliminary Antitumor Activity Partial response (PR) 33% (3 confirmed, 4 unconfirmed) Stable disease (SD) 52% (11) Common treatment-related adverse events elevated CPK and creatinine; skin, hematologic and GI events; edema and fatigue Determination of a Phase 2 dose & schedule are ongoing Binimetinib (single agent) advancing in Phase 3 NRAS mutant melanoma trial (NEMO); projected regulatory filing 2015 Potential for binimetinib beyond single agent in combinations NRAS mutant melanoma has poor prognosis with no approved targeted therapies 5 Investigational compound LEE011 discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals

6 ASCO Investigational Compounds Binimetinib + Novartis BYL719 (PI3Kα) Phase 1b Dose Escalation ASCO 2014 POSTER RAS or BRAF-mutant solid tumors (N=58) (>10 types incl. KRASm ovarian, NRASm melanoma, KRASm endometrial) Demonstrated Preliminary Clinical Activity in KRAS-mutant Ovarian Cancer KRAS-mutant ovarian cancer (n=4) Partial response (PR) 75% (3 confirmed) Overall Study Population (N=58) MTD Binimetinib 45 mg BID + BYL mg QD Partial response (PR) 7% (4) Stable disease (SD) 30% (17) Most common dose limiting toxicities and adverse events overall Gastrointestinal events and rashes 6 Investigational compound BYL719 discovered by Novartis Institutes for BioMedical Research

7 ASCO Selumetinib in NF1 Pediatric Patients Early Encouraging Clinical Activity, Planning Phase 2 ASCO 2014 POSTER Phase 1 MTD Partial response (PR) (defined by NCI investigators as a PN volumetric decrease of 20% using MRI) Common adverse events NF1 & PN Patients (N=18) Neurofibromatosis type 1 (NF1) & Plexiform Neurofibromas (PNs) 20 mg/m 2 /dose BID (50% of adult recommended dose) 61% (11 out of 18) Acneform rash, asymptomatic CK elevation, nausea, vomiting, diarrhea, abdominal pain & fatigue; all toxicities reversible All patients remain on trial after a median of 9 cycles (range, 3-34) 7

8 MEK Programs

9 Binimetinib (MEK162) (Novartis) Three Phase 3 Studies Underway KEY DEAL TERMS Potential Royalty: Yes Potential Milestones Remaining: $408M Structure: Co-develop (reasonably capped costs) & Co-detail in U.S. FIRST INDICATION ADDITIONAL PIVOTAL TRIALS TOTAL TRIALS NEMO / NRAS-mutant Melanoma (20% of mel) PFS; n=393; 2:1 randomized vs. DTIC; projected regulatory filing 2015 COLUMBUS / BRAF-mutant Melanoma (40% of mel) PFS; n=900; 1:1:1 randomized with 1) Novartis BRAF inhibitor plus binimetinib and 2) Novartis BRAF inhibitor as monotherapy 3) Vemurafenib projected regulatory filing 2016 MILO / Low-Grade Serous Ovarian Cancer PFS; n=300; 2:1 randomized vs. physicians choice chemo; projected regulatory filing trials on-going or planned ENROLLING ENROLLING ENROLLING 9

10 Binimetinib Development Pipeline Selected Trials Three Phase 3 Studies Underway INDICATION COMBINATION DRUG EST. PATIENT PHASE 1 PHASE 1B PHASE 2 PHASE 3 NRAS melanoma Single agent 393 LGS Ovarian Cancer Single agent 300 BRAF V600+ melanoma BRAF inhibitor 900 NEMO Phase 3 FPFV July 2013 MILO Phase 3 FPFV June 2013 COLUMBUS Phase 3 FPFV September 2013 Noonan syndrome Single agent <100 RAS/RAF/MEK activated tumors Single agent <100 RAS or BRAF+ solid tumors PI3Kα selective inhibitor <100 Solid tumors pan-pi3k inhibitor <100 NRAS melanoma CDK inhibitor <100 Uveal Melanoma Protein kinase C inhibitor <100 Solid tumors Ganitumab <100 Ovarian cancer Paclitaxel <100 Mutant or wild-type RAS mcrc Panitumumab <100 Solid tumors / Japan Single agent < *Investigator-sponsored trials and clinical pharmacology studies not listed above Registration studies Array-sponsored Novartis-sponsored

11 Selumetinib (AstraZeneca) Phase 3 and Pivotal 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 ENROLLING ADDITIONAL PIVOTAL TRIALS SELECT-1 / KRAS-mutant NSCLC (20-25% of NSCLC) with docetaxel; PFS; n=634; 1:1 randomization vs. docetaxel plus placebo; projected primary data July 2016 ENROLLING CYTOTOXIC COMBINABILITY ASTRA / Thyroid Cancer with RAI; Complete remission rate; n=228, 1:1 randomized vs. placebo; projected primary data June 2016 Selumetinib combines successfully with docetaxel & other chemo at MTD ENROLLING 11

12 Selumetinib Development Pipeline Selected Trials Phase 3 / Pivotal Studies Underway INDICATION COMBINATION DRUG EST. PATIENT PHASE 1 PHASE 1B PHASE 2 PHASE 3 KRAS NSCLC Docetaxel 634 Thyroid Cancer Radioactive Iodine Therapy 304 Uveal Melanoma Dacarbazine 152 Unselected 2 nd -line+ NSCLC Erlotinib, MK-2206, sorafenib 450 SELECT-1 ASTRA Pivotal Trial SUMIT Pivotal Trial BATTLE-2 KRAS/NRAS/HRAS/BRAF NSCLC NSCLC MK-2206, lapatinib, erlotinib, sunitinib Selumetinib,AZD2014, AZD4547, AZD5363, AZD8931, vandetanib, erlotinib or pemetrexed 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 Pancreatic Cancer MK2206 or FOLFOX 133 Biliary Tract Cancer Cisplatin, gemcitabine <100 Neurofibromatosis Single Agent <100 New trials since last quarter 12 AZ Investment decision in 1 st Line KRAS NSCLC Registration studies Broad effort in NSCLC

13 Filanesib (ARRY-520) in Multiple Myeloma

14 [AAG] (g/l) Filanesib (ARRY-520) Novel Approach in MM. Highly selective, targeted KSP inhibitor with a novel mechanism of action distinct from currently approved drugs to treat MM May preferentially act on hematopoietic cells over epithelial cells based on MCL-1 survival dependence Single agent activity demonstrated in Phase 2 trial 16% ORR in heavily pre-treated patients, 24% ORR in AAG-selected pop. Filanesib is active in patients resistant to new IMiD & PIs 1 In low AAG myeloma patients with prior Pomalyst and/or Kyprolis and/or Ixazomib, filanesib showed 31% ORR Filanesib enhances activity of Proteasome Inhibitors High [AAG] Chart Presented at ASH 2012 Partial Response (n=12) Minimal Response (n=4) 14 1 ARRAY Trial, ASH 2013; patients in combination with dexamethasone Time on Treatment (months) AAG Cutoff 1.1 g/l in Array ELISA was qualitatively assigned

15 Filanesib New Combination Data (ASH 12/2013) Filanesib + Kyprolis PUBLISHED ASH December 2013 HEAVILY PRE- TREATED POPULATION DOSING Velcade-refractory or intolerant Revlimid-refractory or intolerant Prior filanesib or Kyprolis 100% 80% 30% Maximum Planned Dose identified; Expansion on-going with increased doses of Kyprolis Filanesib + Velcade Pretreated with Velcade and Revlimid Velcade refractory Revlimid refractory Maximum Planned Dose identified, Expansion on-going with two filanesib regimens 100% 42% 68% CLINICAL ACTIVITY Overall Response Rate (ORR) PR: Clinical Benefit Rate (CBR) MR: 37% 63% ORR (filanesib patients at 1.25 mg/m 2 ): - ORR (PI-refractory patients): - ORR (PI-sensitive patients): - CBR (PI-sensitive patients): 42% 30% 63% 88% SAFETY Well tolerated with minimal non-heme AEs Hematologic toxicity is transient, non cumulative and manageable with supportive care ORR Kyprolis SA in Vel.-refractory patients*: ~16% Well tolerated with manageable non-heme AEs Incidence of all Gr 3/4 non-heme AEs < 20% Hematologic toxicity is transient, non cumulative and manageable with supportive care Filanesib Enhances Activity of Proteasome Inhibitors 15 *Kyprolis registration trial

16 Filanesib Currently Focused on PI Combo & Single Agent in RRMM Providing Clear Path to Market Pivotal Trials Enrolling and/or Announced Front-Line Relapsed/Refractory Novel Agents +Velcade +Revlimid +Velcade +Kyprolis +Pomalyst +Revlimid Single Agent Filanesib (KSP) Panobinostat (HDAC) Ixazomib (oral PI) Elotuzumab (CS1) Daratumumab (CD38) Pomalyst (IMiD) Kyprolis (PI) 16 Filanesib single agent trial designed to support expanded label as part of broader filing

17 Filanesib Global Development Plan in RRMM Today Confirm Combinability FACTOR PHASE 3 KYPROLIS +/- FILANESIB Primary: PFS Secondary: ORR, low AAG, OS Size: several hundred patients, global sites PHASE 2 KYPROLIS +/- FILANESIB Primary: PFS Secondary: low AAG Size: 75 patients, US sites AfFIRM PHASE 2 FILANESIB SINGLE AGENT Primary: ORR in low AAG patients Size: 160 patients, global sites 17

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

19 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 mutation 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

20 p38 Activation and LMNA-related DCM Stress Extracellular RAC1 MLK1 CDC42 Cytoplasm MKK3, 6 ARRY-797: p38 Inhibitor Nuclear Envelope Transcription factors p38 MAPK p38 MAPK RNA binding proteins LMNA Genetic Mutation Stress DNA Transcription / Translation p53 MAPKAP-K2 and K3 ATF2 Fax MEF2 Bax Apoptotic/survival pathways and cardiomyocyte remodeling factors

21 ARRY-797 Proof-of-Concept Trial Enrolling LMNA-Related DCM LMNA-Related DCM patients N=12 ARRY-797 (Dose 1) ARRY-797 (Dose 2) Primary Endpoint: Change from baseline in 6-minute walk test (12 weeks) Secondary Endpoints: Left and right ventricular function, Safety, Quality of Life & Pharmacokinetics Sites: Brigham and Women s Hospital/Harvard Johns Hopkins University Meriter Wisconsin Heart University of Colorado Preliminary results from this study expected by the end of

22 Catalysts

23 2014 Upcoming Catalysts DRUG INDICATION(S) STATUS NEXT MILESTONE BINIMETINIB Binimetinib (MEK162) (Novartis) BRAF Mel. (COLUMBUS) NRAS Mel. (NEMO) LGSOC (MILO) PH 3 Three Phase 3 trials enrolling Projected regulatory filing in 2015 FILANESIB Filanesib (ARRY-520) Multiple Myeloma PH 2 Phase 3 initiation in 2014 PROGRAMS WITH NEAR TERM CATALYSTS Selumetinib (AstraZeneca) NSCLC (SELECT-1) Thyroid Cancer (ASTRA) Uveal Melanoma (SUMIT) PH 3 ARRY-797 LMNA-related DCM PH 2 ARRY-614 MDS PH 1 Three Phase 3 / pivotal trials enrolling Projected regulatory filing in 2015 Phase 2 enrolling Preliminary results expected end of 2014 Maturing data - regulatory discussions in 2014 ARRY-380 Breast Cancer PH 2 (Oncothyreon) Three Phase 1b combination trials ongoing LOXO-101 Cancer PH 1 Phase 1 enrolling (Loxo Oncology) KEY CONFERENCES ASH AAAAI 23 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

24 Inventing, Developing & Commercializing Targeted Small Molecule Drugs in Cancer & Inflammatory Disease 24