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
European Partner Selection Expected in 2015
Initial regulatory submissions are expected in 2016 for both products
1H 2015
2H 2015
1H 2016
2H 2016
NEMO
Top-Line
Results
COLUMBUS
Part 1
Top-Line
Results
MILO
Top-Line
Results
PROJECTED
REGULATORY
FILINGS
PHASE 3
ENROLLMENT
AND RESULTS
PHASE 1 / 2
DATA
AVAILABILITY
3
NEMO LPFV
COLUMBUS
Part 1 LPFV
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
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.
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Previously Published MEK/BRAF Safety Profile &
Clinical Activity
Trametinib + dabrafenib 1
Trametinib + dabrafenib 2 Cobimetinib + vemurafenib 3
Novartis – COMBI-D (n=210) Novartis – COMBI-V (n=352)
Roche - coBRIM (n=247)
SELECT
ADVERSE
EVENTS
OF
INTEREST
Fever
51%
53%
26%
Rash
23%
22%
39%
Diarrhea
24%
32%
57%
Chills
30%
31%
NR (<20%)
Hypertension
22%
26%
NR (<20%)
NR (<10%)
4%
28%
Photosensitivity
NR = Not Reported
COMBI-D
(n=210)
ORR
(CR + PR)
5
1
BRAFi
naive
67%
COMBI-V
(n=352)
64%
Long et al N Engl J Med. 2014; 2 ESMO 2014; 3 Larkin et al N Engl J Med. 2014
coBRIM
(n=247)
68%
ASCO 2015 Oral Presentation:
Ph1/2 LGX + MEK in BRAFmut 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)
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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
Binimetinib+Encorafenib+Third Agent - LOGIC-2
BRAF Melanoma Data Expected in 2015
Patient enrollment on-going
N=140
Group A
BRAF & MEK naïve
patients
Group B
Patients with any
BRAF/MEK combo or
single agents (non-naïve)
Group C
Patients prev. in
Columbus, LOGIC1,
CMEK162X2110, or
Group A (non-naive)
PART 2
PART 1
Group A
Binimetinib +
Encorafenib+third
agent
Group A
Binimetinib +
Encorafenib
Group B
Run-in Binimetinib
+ Encorafenib
After progressive
disease, genetic
assessment performed
to determine
combination
Group C
Optional Binimetinib
+ Encorafenib
Group B
Binimetinib +
Encorafenib+third
agent
Group C
Binimetinib +
Encorafenib+third
agent
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
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Part 2 Third agent: LEE011 (CDK 4/6 inhibitor), BGJ398 (pan FGFR inhibitor), BKM120 (pan
PI3K inhibitor) or INC280 (c-MET inhibitor)
Binimetinib & Encorafenib
Three Phase 3 Studies Underway
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
ENROLLMENT
COMPLETE
ENROLLMENT
COMPLETE
Part 1
ENROLLING
ENROLLING
PFS; n=360; 2:1 randomized binimetinib vs. physicians
choice chemo (crossover permitted); projected regulatory filing 2017
TOTAL TRIALS
8
35 active trials
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
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
a “NRAS
Mutation Status is an Independent Prognostic Factor in Metastatic Melanoma,” Cancer . 2012 August 15; 118(16): 4014–4023
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).
b
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MEK & BRAF Opportunities
Ras/Raf/MEK/Erk pathway mutations implicated in multiple cancer indications
Mutation Prevalence
100000
50000
40000
3 Encorafenib
and/or
Binimetinib
Pivotal Trials
Underway in
Selected Cancer
Populations
Mutation
Other (NF1, SPRED,
SOS1)
GNAQ/GNA11
30000
BRAF
20000
NRAS
10000
KRAS
0
NSCLC
Thyroid
Ovarian Melanoma Ocular Colorectal Pancreatic
(322,000)1 (231,000) 3 (43,000) (30,000) Melanoma (213,000) (65,000) 2
(11,000)
Indication (US Prevalence)
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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
Ph. 1 BRAF-mut. mCRC – Nov. 2014 EORTC-NCI-AACR
Promising Antitumor Activity & Acceptable Safety
Ph. 1 arm = 54 patients (current data)
Ph. 2 arm = 100 patients (enrolling)
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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
0
4
8
12
16
20
24
28
32
36
40
44
48
52
56
Duration of exposure, weeks
Data cutoff date: February 1, 2015.
60
64
68
72
76
80
84
88
92
Selected Binimetinib & Encorafenib Exploratory
Trials
EST.
PATIENT
INDICATION
DRUG(S)
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
PHASE 1
PHASE 1B
PHASE 2
PHASE 3
LOGIC-2
Binimetinib + Encorafenib
Encorafenib
Binimetinib
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*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
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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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
SELECT-1 / KRAS-mutant NSCLC (20-25% of NSCLC)
ADDITIONAL
PHASE 3 TRIALS
ENROLLMENT
COMPLETE
ENROLLING
with docetaxel; PFS; n=634; 1:1 randomization vs.
docetaxel plus placebo; projected regulatory filing 2017
ASTRA / Thyroid Cancer
ENROLLING
with RAI; Complete remission rate; n=304,
1:1 randomized vs. placebo; projected regulatory filing 2017
CYTOTOXIC
COMBINABILITY
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Selumetinib combines successfully with docetaxel
& other chemo at MTD
Selumetinib Development Pipeline – Selected Trials
Phase 3 Studies Underway
EST.
PATIENT
INDICATION
COMBINATION DRUG
KRAS NSCLC
Docetaxel
634
SELECT-1
Uveal Melanoma
Dacarbazine
128
SUMIT
Thyroid Cancer
Radioactive Iodine Therapy
304
ASTRA
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
Registration studies
Neurofibromatosis - adults
Single Agent
<100
Broad effort in NSCLC
Single Agent
<100
16 Neurofibromatosis - peds
PHASE 1
PHASE 1B
PHASE 2
PHASE 3
BATTLE-2
TATTON
ARRY-797 /
p38 Inhibitor for
LMNA-related DCM
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 451
– Events defined as CV death, heart transplant or major cardiac event
Dilated Cardiomyopathy (DCM)
~250,000 patients
U.S.
Prevalence
Estimate
Idiopathic DCM
120-150,000 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
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
19
Stress
Extracellular
RAC1
Cytoplasm
CDC42
MLK1
MKK3, 6
p38 MAPK
ARRY-797:
p38 Inhibitor
Nuclear
Envelope
p38 MAPK
LMNA
Genetic
Mutation
Stress
Transcription
factors
RNA binding
proteins
DNA Transcription / Translation
p53
ATF2
MEF2
MAPKAP-K2
and K3
Fax
Bax
Apoptotic/survival pathways and
cardiomyocyte remodeling factors
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
DRUG
INDICATION(S)
STATUS
Binimetinib
(MEK162)
LGS Ovarian Cancer
Q2
Q3
Q4
✓NEMO enrolled
NRAS Melanoma
BINIMETINIB
Q1
PH 3
Phase 3 NEMO top-line results
Phase 3 MILO enrollment ongoing
BINIMETINIB &
ENCORAFENIB
Binimetinib
(MEK162)
Encorafenib
(LGX818)
BRAF Melanoma
PH 3
Phase 3 COLUMBUS - Part 2 enrolling
✓BRAF-mel. & GIST data/ASCO
✓TATTON NSCLC data / ASCO
Selumetinib
(AZD6244)
Thyroid Cancer
NRAS, BRAF-mel. & CRC data
Phase 3 SUMIT top-line results*
NSCLC
SELUMETINIB
✓COLUMBUS
Part 1 enrolled
PH 3
Phase 3 SUMIT projected regulatory filing*
(AstraZeneca)
NF-1 data later in 2015*
Uveal Melanoma
Phase 3 SELECT-1 and ASTRA enrollment ongoing
FILANESIB
ARRY-797
Filanesib
(ARRY-520)
Multiple Myeloma
PH 2
Generating data from single-agent & Kyprolis-combo Phase 2 trials
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
Inventing, Developing
& Commercializing
Targeted Small Molecule
Drugs in Cancer
www.arraybiopharma.com
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