Drugs in Cancer Jefferies 2015 Global Healthcare Conference Ron - - PowerPoint PPT Presentation

Developing & Commercializing Targeted Small Molecule Drugs in Cancer

Jefferies 2015 Global Healthcare Conference Ron Squarer, Chief Executive Officer June 2, 2015

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 1995. 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.

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Path to Commercialization Upcoming Catalysts for Binimetinib & Encorafenib

PROJECTED REGULATORY FILINGS PHASE 1 / 2 DATA AVAILABILITY PHASE 3 ENROLLMENT AND RESULTS

Planned publications for 2016 TBD

European Partner Selection Expected in 2015 Initial regulatory submissions are expected in 2016 for both products

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

NEMO LPFV COLUMBUS Part 1 LPFV

NEMO Top-Line Results COLUMBUS Part 1 Top-Line Results MILO Top-Line Results

1H 2015 2H 2015 1H 2016 2H 2016

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Binimetinib & Encorafenib Clinical Data Presentations

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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 platinum- resistant 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.

Previously Published MEK/BRAF Safety Profile & Clinical Activity

1 Long et al N Engl J Med. 2014; 2 ESMO 2014; 3 Larkin et al N Engl J Med. 2014

NR = Not Reported Fever Rash Diarrhea Chills

51% 53% 23% 22% 24% 32% 30% 31% 22% 26%

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Cobimetinib + vemurafenib3 Roche - coBRIM (n=247) Trametinib + dabrafenib2 Novartis – COMBI-V (n=352)

26% 39% 57% NR (<20%) NR (<20%)

Hypertension

SELECT ADVERSE EVENTS OF INTEREST

Photosensitivity

NR (<10%) 4% 28%

ORR (CR + PR)

BRAFi naive

67% 64% 68%

COMBI-D (n=210) coBRIM (n=247) COMBI-V (n=352) Trametinib + dabrafenib1 Novartis – COMBI-D (n=210)

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) Median Progression Free Survival 11.3 months

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ASCO 2015 Oral Presentation: Ph1/2 LGX + MEK in BRAFmut melanoma/BRAFi-naïve pts

Binimetinib+Encorafenib+Third Agent - LOGIC-2 BRAF Melanoma Data Expected in 2015

Primary endpoint: Overall Response Rate (Part 2) Secondary endpoint: Safety 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) Group A Binimetinib + Encorafenib Group C Optional Binimetinib + Encorafenib Group B Run-in Binimetinib + Encorafenib

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Group A Binimetinib + Encorafenib+third agent Group C Binimetinib + Encorafenib+third agent Group A

BRAF & MEK naïve patients

Group C

Patients prev. in Columbus, LOGIC1, CMEK162X2110, or Group A (non-naive)

Group B

Patients with any BRAF/MEK combo or single agents (non-naïve)

Patient enrollment on-going N=140

Group B Binimetinib + Encorafenib+third agent

PART 1 PART 2

After progressive disease, genetic assessment performed to determine combination

FIRST INDICATION

NEMO / NRAS-mutant Melanoma (20% of mel)

PFS; n=393; 2:1 randomized binimetinib vs. DTIC; projected regulatory filing first half of 2016

ADDITIONAL PIVOTAL TRIALS

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

MILO / Low-Grade Serous Ovarian Cancer

PFS; n=360; 2:1 randomized binimetinib vs. physicians choice chemo (crossover permitted); projected regulatory filing 2017

TOTAL TRIALS

35 active trials

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Binimetinib & Encorafenib Three Phase 3 Studies Underway

ENROLLMENT COMPLETE ENROLLING ENROLLMENT COMPLETE Part 1 ENROLLING

a “NRAS Mutation Status is an Independent Prognostic Factor in Metastatic Melanoma,” Cancer . 2012 August 15; 118(16): 4014–4023 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, post-

baseline 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).

Phase 2 - Binimetinib in Advanced NRAS Melanoma Median Overall Survival (mOS) Encouraging

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• 117 NRAS+ melanoma patients
• 12.2 months mOS

– Historical published prognosis for NRAS+ melanoma patients is 8.2 monthsa

• 3.6 months mPFS

– Confirms interim results reported at ASCO 2012

• 14.5% 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

10000 20000 30000 40000 50000

NSCLC (322,000) Thyroid (231,000) Ovarian (43,000) Melanoma (30,000) Ocular Melanoma (11,000) Colorectal (213,000) Pancreatic (65,000)

Other (NF1, SPRED, SOS1) GNAQ/GNA11 BRAF NRAS KRAS

MEK & BRAF Opportunities

Ras/Raf/MEK/Erk pathway mutations implicated in multiple cancer indications

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Mutation Indication (US Prevalence)

Data Source: Sanger Institute COSMIC Database (Nov 6, 2012)

1 Mascaux C et al. Br J Cancer 2005;92:131–9 2 Eser S et al. Br J Cancer 2014;111:817-822 3 Majority of thyroid patients treated with surgery & radioactive iodine

Mutation Prevalence

100000

3 Encorafenib and/or Binimetinib Pivotal Trials Underway in Selected Cancer Populations

3 2

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• Ph. 1 BRAF-mut. mCRC – Nov. 2014 EORTC-NCI-AACR

Promising Antitumor Activity & Acceptable Safety

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• Ph. 1 arm = 54 patients (current data)
• Ph. 2 arm = 100 patients (enrolling)

Data cutoff date: February 1, 2015.

20 16 12 4 24 32 68 72 76 84 80 88 92 64 60 52 48 44 36 Duration of exposure, weeks 28 40 56 8

Complete response (CR) Partial response (PR) Stable disease (SD) Progressive disease (PD) Unknown Ongoing

• Ph. 1 BRAF-mut. mCRC – April 2015 AACR Annual Meeting

31% of patients received treatment benefit for more than 1 year Phase 1, Dual Combination Arm (encorafenib + cetuximab)

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 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

Selected Binimetinib & Encorafenib Exploratory Trials

LOGIC-2

*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

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Binimetinib Encorafenib Binimetinib + Encorafenib

Encorafenib & Binimetinib Status Update Transactions closed on March 2, 2015

• 35 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

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KEY DEAL TERMS

Potential Royalty: Double-digits Potential Milestones Remaining: $70M Structure: AZ responsible for global development & commercialization

FIRST INDICATION

SUMIT / Uveal Melanoma

with dacarbazine; PFS; n=128; 1:1 randomization vs. dacarbazine plus placebo; projected regulatory filing 2015

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

ASTRA / Thyroid Cancer

with RAI; Complete remission rate; n=304, 1:1 randomized vs. placebo; projected regulatory filing 2017

CYTOTOXIC COMBINABILITY

Selumetinib combines successfully with docetaxel & other chemo at MTD

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Selumetinib (AstraZeneca) Phase 3 Studies Underway

ENROLLING ENROLLING ENROLLMENT COMPLETE

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 2nd-line+ NSCLC Erlotinib, MK-2206, sorafenib 450 KRAS/NRAS/HRAS/BRAF NSCLC MK-2206, lapatinib, erlotinib, sunitinib 600 NSCLC Selumetinib,AZD2014, AZD4547, AZD5363, AZD8931, vandetanib, erlotinib or pemetrexed 650 KRAS Wildtype or Unknown Non-Squamous NSCLC Pemetrexed, cisplatin 140 Unselected 1st-line NSCLC Gemcitabine and cisplatin <100 Unselected 1st-line NSCLC (KRAS sub-analysis) Paclitaxel, carboplatin, pemetrexed, cisplatin <100 Unselected 2nd-line+ NSCLC (Japan) Docetaxel <100 EGFR Advanced NSCLC AZD9291+selumetinib, AZD9291+MEDI4736, or AZD9291+AZD6094 300 Advanced NSCLC MEDI4736+selumetinib+docetaxel MEDI4736+gefitinib MEDI4736+AZD9291 MEDI4736+tremelimumab <100 Pancreatic Cancer MK2206 or FOLFOX 133 Neurofibromatosis - adults Single Agent <100 Neurofibromatosis - peds Single Agent <100

Selumetinib Development Pipeline – Selected Trials Phase 3 Studies Underway

SELECT-1

Registration studies

SUMIT BATTLE-2

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ASTRA

Broad effort in NSCLC

TATTON

ARRY-797 / p38 Inhibitor for LMNA-related DCM

LMNA-related Dilated Cardiomyopathy (DCM)

Dilated Cardiomyopathy (DCM) ~250,000 patients Idiopathic DCM 120-150,000 patients LMNA-DCM 6-8,000 patients

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 451

– Events defined as CV death, heart transplant or major cardiac event

U.S. Prevalence Estimate

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

<1,000 pts Diagnosed

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

• 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 LMNAN195K model of DCM

• Physician-sponsored single-patient IND

indicated that ARRY-797 treatment has been associated with cardiac function improvements and was well tolerated

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DNA Transcription / Translation

ARRY-797: p38 Inhibitor

Cytoplasm Extracellular Nuclear Envelope p53 MAPKAP-K2 and K3 ATF2 Fax MEF2 Bax MLK1 RAC1 p38 MAPK p38 MAPK MKK3, 6 CDC42

Stress

Transcription factors RNA binding proteins

Apoptotic/survival pathways and cardiomyocyte remodeling factors LMNA Genetic Mutation Stress

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

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Value Drivers

Array Expected Product Portfolio Value Drivers

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

Q1 Q2 Q3 Q4 DRUG INDICATION(S) STATUS ARRY-797 FILANESIB Filanesib (ARRY-520) Multiple Myeloma

PH 2

BINIMETINIB & ENCORAFENIB Binimetinib (MEK162) Encorafenib (LGX818) BRAF Melanoma

PH 3

ARRY-797 LMNA-related DCM

PH 2

SELUMETINIB Selumetinib (AZD6244)

(AstraZeneca)

PH 3

NSCLC Thyroid Cancer Uveal Melanoma

Phase 3 SUMIT projected regulatory filing* Phase 3 SELECT-1 and ASTRA enrollment ongoing Generating data from single-agent & Kyprolis-combo Phase 2 trials Additional results *Based on projections from AstraZeneca

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COLUMBUS Part 1 enrolled Phase 3 MILO enrollment ongoing Phase 3 NEMO top-line results

BINIMETINIB Binimetinib (MEK162)

PH 3

BRAF-mel. & GIST data/ASCO

✓

Phase 3 COLUMBUS - Part 2 enrolling Phase 3 SUMIT top-line results* TATTON NSCLC data / ASCO

NRAS Melanoma LGS Ovarian Cancer

NEMO enrolled

✓

NF-1 data later in 2015* NRAS, BRAF-mel. & CRC data

✓ ✓

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www.arraybiopharma.com

Inventing, Developing & Commercializing Targeted Small Molecule Drugs in Cancer