J.P. Morgan 34
th
Annual
Healthcare Conference
Ron Squarer
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, 2015,
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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Array’s Top Priority
Binimetinib & Encorafenib Development & Commercialization
…WITH IMPORTANT VALUE DRIVERS AHEAD IN 2016
Regained rights to binimetinib and acquired global rights to encorafenib along with $100 million+ payment from Novartis
Completed Pierre Fabre collaboration including $30 million
upfront, $425 million potential milestones and robust, tiered, double-digit royalties
Array retains exclusive rights in key markets including U.S. & Japan
Pierre Fabre has exclusive rights in other geographies, including
Europe, Asia & Latin America
NRAS-mutant melanoma Phase 3 (NEMO) trial achieved primary endpoint
Published clinical results for
BRAF-mutant colorectal cancer Phase 1/2 BRAF-mutant melanoma Phase 2 (LOGIC2)
NRAS-mutant melanoma Phase 1/2 (CDK 4/6 combo)
SECOMBIT trial will address sequential use of MEK+RAF with
PD-1+CTLA4 in BRAF-mutant melanoma
Phase 3/NRAS-mutant melanoma
Present full results
File for regulatory approval
Phase 3 Part 1/BRAF-mutant melanoma
Announce results
Present full results
File for regulatory approval
Phase 3/LGS ovarian cancer
Complete enrollment
BRAF-mutant metastatic colorectal cancer
Present update from Phase 2 expansion
Initiate Phase 3 global registration trial
NEMO
Meets Primary Endpoint
NEMO is a pivotal Phase 3 trial comparing binimetinib to dacarbazine in patients with NRAS-mutated melanoma
20% of patients with metastatic melanoma have NRAS-mutations
NRAS diagnostic being developed in collaboration with Qiagen
NEMO study met its primary endpoint of improving progression free survival (PFS) compared with dacarbazine treatment
Hazard ratio (HR) 0.62, [95% CI 0.47-0.80], p < 0.001
Median PFS on the binimetinib arm was 2.8 months versus 1.5 months on dacarbazine arm
Binimetinib appeared to be generally well-tolerated
Adverse events reported were consistent with results from previous, earlier phase binimetinib studies in NRAS-mutant melanoma patients
No new safety signals were seen
More data to be presented at medical conference in 2016 including
PFS, overall survival (OS), overall response rate (ORR), safety
Prespecified subgroup analyses including outcomes in patients who received prior treatment with immunotherapy
Binimetinib Phase 3 Study
NEMO Meets Primary Endpoint
Positive results from the NEMO trial further demonstrate the
potential of binimetinib to provide an important new treatment option for patients with advanced/unresectable
NRAS-mutant melanoma.
Binimetinib + Ribociclib – 28-Day Regimen
Promising Preliminary Clinical Activity in NRAS-Mutant Melanoma
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ECC/ESMO 2015: A Phase 1b/2 study of ribociclib (LEE011; CDK4/6 inhibitor) in combination with binimetinib (MEK162; MEK inhibitor) in patients with NRAS-mutant melanoma naïve to BRAFi treatment (Abstract #3300)
aRate includes unconfirmed CR/PR
Response n (%) All 28-Day Regimen Patients n=22 All 21-Day Regimen Patients n=23 Evaluable Patients 22 22 Complete Response 0 0
Partial Response Confirmed PR Unconfirmed 5 (23) 4 (18) 3 (14) 1 (5) Stable Disease (SD) 9 (41) 11 (50) Progressive Disease 3 (14) 4 (18) Unknown 1 (5) 3 (14)
Overall Response Rate (ORR)a 9 (41) 4 (18)
Disease Control Rate 18 (82) 15 (68) Median Progression
Free Survival, Months 6.7 4
Individual Patient Responses
Observed activity did not appear to be driven by higher doses of ribociclib as patients in lowest dose cohort of 200mg ribociclib + 45mg BID‡binimetinib achieved a 56% overall response rate (ORR)
Safety: Binimetinib and ribociclib are combinable in NRAS-mutant melanoma patients
The most common treatment-related adverse events included elevated
creatine phosphokinase (CPK), skin and gastrointestinal events
LOGIC2/SECOMBIT
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LOGIC2 – Binimetinib + Encorafenib + Third Agent
BRAF-Mutant Melanoma Study Design
GROUP A
BRAF- and MEK-naïve patients
GROUP B
Patients with any BRAF/MEK combo or single agents (non-naïve)
GROUP C
Patients previously in COLUMBUS, LOGIC1, CMEK162X2110, or Group A
(non-naïve)
GROUP A
Binimetinib + Encorafenib
GROUP B Run-in Binimetinib + Encorafenib
GROUP C
Optional Binimetinib + Encorafenib Patient Enrollment
on-going n=140
Part 1 n=89 as of 7/1/15
After progressive disease, genetic assessment performed to
determine combination
Binimetinib + Encorafenib + LEE011 (CDK 4/6 inhibitor) Part 2 n=20 as of 7/1/15 Binimetinib + Encorafenib + BGJ398 (pan FGFR inhibitor) Binimetinib + Encorafenib + BKM120 (pan PI3K inhibitor)
Binimetinib + Encorafenib + INC280 (c-MET inhibitor)
Primary Endpoint: Overall response rate (ORR) (Part 2)
Secondary Endpoint: Safety
After Progressive Disease 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
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Combination of binimetinib and encorafenib demonstrated encouraging preliminary clinical activity in
BRAFi/MEKi naïve patients
1ECC/ESMO 2015: LOGIC2: Phase 2, multi-center, open-label study of sequential encorafenib/binimetinib combination followed by a rational combination with targeted agents after progression, to overcome resistance in adult patients with locally-advanced or metastatic BRAF
V600 melanoma (Abstract #3310); 2Includes confirmed/unconfirmed responses; 3ORR=CR/PR, 4DCR=CR/PR or SD *QD – Once Daily; †BID – Twice Daily
Clinical trial number NCT02159066
LOGIC2 – Binimetinib + Encorafenib Part 1
Encouraging Preliminary Clinical Activity
Phase 2 (as of 7/1/15)
Group A (MEKi + BRAFi Naïve)
Encorafenib 450mg QD* + Binimetinib 45mg BID† n=45
AE, n (%)
Binimetinib 45mg BID/Encorafenib 450mg QD BRAFi/MEKi Naïve Patients
n=40
Overall Response Rate (ORR)2,3 68%
Disease Control Rate (DCR)2,4 95%
6-Month Median Progression Free Survival (PFS) 79%
(Note: 96% of patients continued to receive study treatment as of data cutoff)
Complete Response (CR)2 3% (1)
Partial Response (PR)2 65% (26)
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Differentiated Safety: 12% pyrexia, 7% rash and no photosensitivity
Data cutoff date: July 1, 2015.
*CPK – Creatine phosphokinase; †QD – Once Daily; ‡BID – Twice Daily
Clinical trial number NCT02159066
LOGIC2 – Binimetinib + Encorafenib Part 1
Good Tolerability
Phase 2 (as of 7/1/15)
Group A (MEKi + BRAFi Naïve)
Encorafenib 450mg QD†+ Binimetinib 45mg BID‡
n=45
Group B (Prior BRAFi and/or MEKi) Encorafenib 450mg QD + Binimetinib 45mg BID
n=43
All Patients n=89
AE, n (%) All Grades n (%) Grade 3/4 n (%) All Grades n (%) Grade 3/4 n (%) All Grades n (%) Grade 3/4 n (%)
Total 42 (93) 16 (36) 39 (91) 21 (49) 82 (92) 37 (42) Nausea 12 (27) 3 (7) 12 (28) 2 (5) 24 (27) 5 (6) Diarrhea 14 (31) 0 8 (19) 0 23 (26) 0 Fatigue 9 (20) 1 (2) 12 (28) 2 (5) 22 (25) 3 (3) Retinopathy 14 (31) 0 7 (16) 0 21 (24) 0 Vomiting 7 (16) 1 (2) 7 (16) 0 15 (17) 1 (1) Blood CPK increased 11 (24) 1 (2) 3 (7) 0 14 (16) 1 (1) Pyrexia 5 (11) 1 (2) 6 (14) 0 11 (12) 1 (1) Abdominal Pain 7 (16) 0 3 (7) 0 10 (11) 0 Anemia 4 (9) 1 (2) 6 (14) 3 (7) 10 (11) 4 (5) Vision blurred 5 (11) 0 4 (9) 0 9 (10) 0
1Long et al ASCO Oral 2015; 2ESMO/ECC 2015; 3Product label; 4Larkin et. al. ASCO Oral 2015
*ORR = Overall Response Rate (Complete Response (CR) + Partial Response Rate (PR)
Published MEK/BRAF Data in BRAF-Mutant Melanoma
Safety Profile & Clinical Activity
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Novartis – COMBI-D Trametinib + Dabrafenib1 n=209 Novartis – COMBI-V Trametinib + Dabrafenib2 n=350 Roche – coBRIM Cobimetinib + Vemurafenib3 n=247 Select Adverse Events of Interest Fever 52% 55% 28% Rash 24% 24% 16% Diarrhea 18% 34% 60% Chills 28% 33% 10% Hypertension 10% 29% 15% Photosensitivity NR (<10%) 4% 46%
NR = Not Reported COMBI-D n=210 COMBI-V n=251 coBRIM4n=247
New Trial – SECOMBIT/Sequential Combo
Immuno and Target Therapy Study
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Patients with BRAF-Mutant Melanoma
n=230
Ipilimumab + Nivolumab
Binimetinib + Encorafenib
Binimetinib + Encorafenib Progression
2 Cycles Progression Binimetinib + Encorafenib
Randomization
Ipilimumab + Nivolumab
Binimetinib + Encorafenib
Ipilimumab + Nivolumab
Primary Endpoint: Overall survival (OS)
Key Secondary Endpoint:Progression free survival (PFS)
One of the most comprehensive studies assessing sequencing strategies for
targeted and immunotherapies in BRAF-mutant melanoma
Evaluate best sequencing approach with combination of target agents (encorafenib + binimetinib) and the combination of immunomodulatory antibodies (ipilimumab + nivolumab) in patients with BRAF-mutant melanoma
Multicenter, international cooperative group trial: Clinical Research Technology and Fondazione Melanoma Onlus; supported jointly by Bristol-Myers Squibb and Array (via Novartis)
Encorafenib
Historically, response rates are very low for either single-agent EGFR or RAF inhibitor therapy in patients
with BRAF-mutant metastatic colorectal cancer (mCRC). Data in this study suggest a synergistic effect for
the combination of encorafenib and cetuximab in this population.
Data cutoff date: May 22, 2015
*Evaluable patients had a tumor assessment at 12 week visit or later and/or started treatment ≥ 13 weeks prior to data cutoff; bIncludes four unconfirmed PRs; cIncludes five unconfirmed PRs. CR and PR were confirmed by
repeat assessments performed ≥ four weeks after initial response
Encorafenib Phase 2 BRAF-Mutant mCRC
Encouraging Clinical Activity
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Encorafenib + Cetuximab n=42
Encorafenib + Alpelisib (BYL719, PI3K Inhibitor) + Cetuximab (EGFR Inhibitor)
n=49
Evaluable Patientsa 38 43
Partial Response Rate (PR) 11 (29%)b 15 (35%)c
Stable Disease (SD) 20 (53%) 19 (44%)
Progressive Disease (PD) 1 (3%) 3 (7%)
Unknown 6 (16%) 6 (14%)
Overall Response Rate (ORR) 11 (29%)b 15 (35%)c
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Across all treatment groups, most AEs were Grade 1 or 2
Data cutoff date: May 22, 2015.
Encorafenib Phase 2 BRAF-Mutant Metastatic Colorectal Cancer
Good Tolerability
Encorafenib + Cetuximab n=42
Encorafenib + Alpelisib + Cetuximab n=49
AE, n (%) All Grades Grade 3/4 All Grades Grade 3/4
Total 37 (88%) 12 (29%) 46 (94%) 24 (49%) Diarrhea 9 (21%) 1 (2%) 19 (39%) 4 (8%) Nausea 13 (31%) 0 18 (37%) 3 (6%) Fatigue 15 (36%) 0 16 (33%) 3 (6%) Hyperglycemia 1 (2%) 0 15 (31%) 7 (14%) Rash 7 (17%) 0 13 (27%) 0 Stomatitis 4 (10%) 0 13 (27%) 2 (4%) Decreased Appetite 9 (21%) 0 11 (22%) 1 (2%) Pruritus 7 (17%) 0 11 (22%) 0 Dry Skin 5 (12%) 0 10 (20%) 0 Maculopapular Rash 1 ( 2%) 0 10 (20%) 2 (4%) Lipase Increased 10 (24%) 7 (17%) 4 ( 8%) 2 (4%)
aESMO GI 2015; bASCO 2015;
Panitumumab: EGFR inhibitor, dabrafenib: RAF inhibitor, trametinib: MEK inhibitor Cetuximab: EGFR inhibitor, vemurafenib: RAF inhibitor, irinotecan: Cytotoxic *ORR (CR + PR) – Overall response rate (complete response rate + partial response rate)
Published BRAF in BRAF-Mutant Metastatic Colorectal Cancer
Safety Profile & Clinical Activity
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Doublet Therapy Panitumumab + Dabrafeniba Novartis – Phase 2 n=20 Triplet Therapy Panitumumab + Dabrafenib + Trametiniba Novartis – Phase 2 n=35 No Doublet Included Triplet Therapy Cetuximab + Vemurafenib + Irinotecanb Roche – Phase 1 n=18 ORR (CR + PR)* 10% 26% 35% Select Adverse Events of Interest Fatigue 45% 51% 94% Nausea 40% 49% 83% Diarrhea 45% 77% 89% Rash 30% 37% 78%
Strategic Collaboration
Array’s Selection Criteria for Strong European Commercial
Partner was Met by Pierre Fabre
Company with Europe as leading geographic priority with robust emerging market capability to provide scale to collaboration
Company with significant footprint in Oncology Development, Sales & Marketing
Company willing to commit significant resources to ensure binimetinib and encorafenib success
Company providing robust downstream economics (royalties) for ready-to-file products
The agreement was reviewed and approved by the European Commission on Competition in December 2015
Strategic Collaboration with Pierre Fabre Oncology
Selection Criteria & Summary of Deal Terms
Benefits to Array $30 million upfront
40% funding for certain future clinical development
Up to $425 million in potential development and commercialization milestones
Robust, tiered double-digit royalties Commercialization Rights
Array retains exclusive rights in: United States
Canada Japan Korea Israel
Pierre Fabre will have exclusive rights in all other geographies, including Europe, Asia and Latin America
Selumetinib
Neurofibromatosis Type 1/
Plexiform Neurofibromas
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that can cause tumors to grow on nerves throughout the body
Most tumors are inoperable
NF1 may lead to blindness, bone abnormalities, cancer, deafness, disfigurement, learning disabilities and excruciating and disabling pain
Plexiform neurofibromas (PN) exhibit the most rapid growth in young children
Early intervention in children with growing PNs may result in the greatest clinical benefit
NF affects one in every 3,000 individuals; 100,000 in the U.S.
NF affects more than cystic fibrosis, Duchenne muscular dystrophy and Huntington’s disease combined
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No Standard Medical Therapies for Patients
with NF1/PN
3 Years
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Selumetinib offers a promising future for the development of effective medical therapies for
neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PNs)
Selumetinib & Other Agents Studied in Phase 2 PN
Selumetinib Is Only Agent With No Progression
Presented June 2015
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All neurofibromatosis type 1 (NF1) patients remained on treatment
Selumetinib in NF1 Pediatric Patients
PR Seen in 67% of Patients
Partial Response (PR)* 67% (16 out of 24)
Progressive Disease (PD)* 0%
Common Adverse Events (AEs) Acneiform rash, asymptomatic CK elevation, GI; all
toxicities reversible
Median Cycle (1 Cycle = 28 Days) 18 (6-43)
Other Observations Improvement in functionReduction in PN related pain and disfigurement *PR and PD – Defined by NCI investigators as a PN volumetric decrease of ≥20% using MRI
Primary Endpoint:Confirmed response rate by volumetric MRI Secondary Endpoint:
PRO: Pain, Quality of Life (QOL), function (all patients)
Disfigurement: Photography (patients with visible PN)
Function: All patients based on PN location – Orbit, airway, motor, bladder, other
PK, PD: Blood cytokines, BM cells – All patients pre-selumetinib and on treatment
Long term safety, bone mineral density, optic glioma
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Neurofibromatosis Type 1/Plexiform Neurofibromas
(NF1/PN) Pediatric Registration Study
Primary Objectives Achieved
Currently Enrolling Patient
s
Phase 1 Dose Escalation
Children 3-18 y/o with NF1 and inoperable PN n=24
Pediatric Registration Study
Children 2-18 y/o with NF1 and inoperable PN Selumetinib
(25mg/m2/dose BID) n=50
Expansion
Immuno-Oncology
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Immunotherapy – Small Molecule Opportunity
Many targets from multiple target classes are implicated in the immunosuppressive state of the tumor microenvironment. Many targets are uniquely suited to small
molecule approaches and not modulation by biotherapeutics
Small molecule target modulation is underexplored in Immuno-Oncology
Collaborating with world-class scientific advisory board (SAB) and leading academic partners to pursue
immuno-oncology programs
SAB includes:
Keith Flaherty (MGH)
Ben Cravatt (TSRI)
David McDermott (BIDMC)
Doug Lauffenburger (MIT)
Kwok- Kin Wong (DFCI/HMS)
Kris Vaddi (Ex-InCyte)
Jedd Wolchok (MSKCC)
Forest White (MIT/Koch)
Trevor Bivona (UCSF)
Peter Hammerman (DFCI/HMS) Axl
Axl
cancer cell
Adapted from Cancers 2015, 7(2), 736-762
Multi-program immuno-oncology collaboration
Leveraging Array’s capabilities and track record in small molecule drug discovery Medicinal Chemistry and Structure Enabled Drug Design
Pharmacology, Pharmaceutics and Pharmacokinetics
Target identification through chemical biology
Leveraging Belfer’s immuno-oncology expertise and connectivity to Dana-Farber Cancer Institute (DFCI) investigators, knowledge base and capabilities for
Target identification and validation
Novel preclinical models for immunotherapeutic drug assessment
Tumor immune infiltrate profiling in clinical samples for mechanistic assessment and patient selection
Array and DFCI scientists discovering innovative
immunotherapies
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New Immuno-Oncology Preclinical Collaboration
Enabling Novel Drug Target Prosecution in Immuno-Oncology
ARRY-797
P38 Inhibitor for LMNA-Related Dilated
Cardiomyopathy (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, ~70% of patients have death, major cardiac event or transplant by age 45
Events defined as cardio vascular (CV) death, heart transplant or major cardiac event
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
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Dilated Cardiomyopathy (DCM) ~250,000 patients Idiopathic DCM 120-150,000 patients Diagnosed <1,000U.S. Prevalence Estimate
LMNA-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 ARRY-797 treatment has been associated with cardiac function improvements and was well tolerated
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Rationale for ARRY-797 in Treatment of LMNA-Related Dilated
DCM
Cytoplasm Extracellular
Stress
Apoptotic/Survival Pathways and
RAC1 CDC42 MLK1 p38 MAPK MKK3, 6 ARRY-797: p38 Inhibitor LMNA Genetic Mutation Stress Nuclear Envelope DNA Transcription/Translation p38 MAPK RNA binding proteins p53 MAPKAP-K2 and K3 ATF2 Fax MEF2 Bax Transcription factors
Primary Endpoints: Change from baseline in 6-minute walk test (12 weeks) Secondary Endpoints
Measures of left and right ventricular function
Ejection fraction (Imaging study directly measures cardiac function); fractional area shortening
Circulating biomarkers of cardiac function
N-Terminal pro-Brain Derived Natriuretic Peptide: Blood test that indirectly measures cardiac wall stress and severity and prognosis in cardiac failure
Disease specific patient reported outcomes: Measures patient perception of improvement in functional status
Others
Trial Sites:Brigham and Women’s Hospital/Harvard, Johns Hopkins University, Meriter Wisconsin Heart, University of Colorado, Ohio
State University, Stanford University
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ARRY-797 Proof-of-Concept Trial
LMNA-Related Dilated Cardiomyopathy (DCM)
Crossover from lower to higher dose allowed for inadequate response
LMNA-Related DCM Patients n=12 ARRY-797 (Dose 1) ARRY-797 (Dose 2)
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ARRY-797 secondary endpoint measures also suggest encouraging activity (NT-proBNP, patient reported
outcomes)
Patient experience out to 48 weeks continues to be encouraging
Compared with Historical Benchmarks, Encouraging Data
Emerging from Ongoing Phase 2 Trial
Product Company Indication ApprovedFDA
ARRY-797 Array LMNA-DCM No
Bosentan Actelion PAH Yes
Idursulfase Shire MPS II Yes
Riociguat Bayer CTEPH & PAH Yes
Elosulfase Alfa BioMarin MPS IVA Yes
Ambrisentan Gilead PAH Yes
Laronidase Genzyme MPS I Yes
0 10 20 30 40 50 Meters
ARRY-797 absolute mean improvement in 6MWT at 12
weeks is encouraging and suggests a path forward when
benchmarked against drugs approved based on 6MWT
Indication(s) Status 1H 2016 2H 2016 Binimetinib & Encorafenib BRAF Melanoma (COLUMBUS) (binimetinib+encorafenib)
Phase 3 COLUMBUS Part 1 Results
Regulatory Submission
NRAS Melanoma (NEMO)
(binimetinib)
Phase 3 Regulatory Submission
NEMO Publication
LGS Ovarian (MILO)
(binimetinib)
Phase 3 Complete Enrollment
BRAF Colorectal Cancer (CRC)
(Encorafenib+other agent(s)
Phase 2/3 Phase 2 BRAF CRC Update
Phase 3 global registration trial (start date TBA)
Selumetinib
NSCLC (SELECT-1)
Phase 3 Registration trial
SELECT-1 Top-Line Results
Thyroid Cancer
(ASTRA) Enrollment Ongoing
NF1 Enrollment Ongoing
ARRY-797 LMNA-related DCM Phase 2 Trial Ongoing
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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