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. 2
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 PROJECTED REGULATORY FILINGS NEMO LPFV COLUMBUS MILO NEMO PHASE 3 Part 1 Top-Line ENROLLMENT Top-Line Top-Line Results AND RESULTS COLUMBUS Results Results Part 1 LPFV • Ph 1/2 NRAS melanoma w/LEE011 ASCO 2015 • Ph 1/2 BRAF PHASE 1 / 2 Planned publications for DATA • Ph 1/2 BRAF melanoma LOGIC-2 Melanoma 2016 TBD AVAILABILITY • Ph 1/2 GIST • Ph 1/2 BRAF CRC w/cetuximab w/imatinib 3
Binimetinib & Encorafenib Clinical Data Presentations Type Phase Indication Title Binimetinib and/or Encorafenib ORAL Phase BRAF-mutant melanoma A phase 1b/2 study of BRAF inhibitor (BRAFi) encorafenib 1b/2 (ENCO) plus MEK inhibitor (MEKi) binimetinib (BINI) in cutaneous melanoma patients naive to BRAFi treatment ORAL Phase Gastrointestinal stromal tumor A phase Ib/II study of MEK162 (binimetinib [BINI]) in combination with imatinib in patients with advanced gastrointestinal stromal 1b/2 tumor A phase 1b dose-escalation study of binimetinib (MEK162) in Poster Phase 1b Epithelial ovarian, fallopian tube or primary peritoneal combination with weekly paclitaxel in patients with platinum- cancer 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. 4
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) 51% 53% 26% Fever 23% 22% Rash 39% SELECT 24% 32% Diarrhea 57% ADVERSE EVENTS OF 30% 31% NR (<20%) Chills INTEREST 26% NR (<20%) Hypertension 22% 4% Photosensitivity NR (<10%) 28% NR = Not Reported COMBI-D COMBI-V coBRIM (n=210) (n=352) (n=247) BRAFi 67% 64% 68% ORR (CR + PR) naive 5 1 Long et al N Engl J Med. 2014; 2 ESMO 2014; 3 Larkin et al N Engl J Med. 2014
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) 62% (34 of 55) Partial response (PR) 13% (7 of 55) Complete response (CR) Stable disease (SD) 22% (12 of 55) Median Progression Free Survival 11.3 months 6
Binimetinib+Encorafenib+Third Agent - LOGIC-2 BRAF Melanoma Data Expected in 2015 Patient enrollment on-going PART 1 PART 2 N=140 Group A Group A Group A Binimetinib + Binimetinib + BRAF & MEK naïve Encorafenib+third patients Encorafenib agent After progressive Group B Group B Group B disease, genetic Binimetinib + Run-in Binimetinib Patients with any assessment performed Encorafenib+third BRAF/MEK combo or + Encorafenib to determine single agents (non-naïve) agent combination Group C Group C Group C Patients prev. in Binimetinib + Optional Binimetinib Columbus, LOGIC1, Encorafenib+third CMEK162X2110, or + Encorafenib agent Group A (non-naive) 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) 7
Binimetinib & Encorafenib Three Phase 3 Studies Underway FIRST INDICATION NEMO / NRAS-mutant Melanoma (20% of mel) ENROLLMENT PFS; n=393; 2:1 randomized binimetinib vs. DTIC; COMPLETE projected regulatory filing first half of 2016 ADDITIONAL COLUMBUS / BRAF-mutant Melanoma (40% of mel) ENROLLMENT PIVOTAL TRIALS PFS; n=900 COMPLETE Part 1: 1:1:1 randomized with Part 1 1) Encorafenib (450mg) plus binimetinib 2) Encorafenib (300mg) as monotherapy 3) Vemurafenib projected regulatory filing 2016 Part 2: 3:1 randomization with ENROLLING 1) Encorafenib (300mg) plus binimetinib 2) Encorafenib (300mg) as monotherapy MILO / Low-Grade Serous Ovarian Cancer ENROLLING PFS; n=360; 2:1 randomized binimetinib vs. physicians choice chemo (crossover permitted); projected regulatory filing 2017 TOTAL TRIALS 35 active trials 8
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 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 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). 9
MEK & BRAF Opportunities Ras/Raf/MEK/Erk pathway mutations implicated in multiple cancer indications 100000 3 Encorafenib Mutation and/or Mutation Prevalence Binimetinib 50000 Pivotal Trials Underway in Other (NF1, SPRED, Selected Cancer 40000 SOS1) Populations GNAQ/GNA11 30000 BRAF 20000 NRAS 10000 KRAS 0 NSCLC Thyroid Ovarian Melanoma Ocular Colorectal Pancreatic 1 3 2 (322,000) (231,000) (43,000) (30,000) Melanoma (213,000) (65,000) (11,000) 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 10
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) 11
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 60 64 68 72 76 80 84 88 92 Duration of exposure, weeks Data cutoff date: February 1, 2015.
Selected Binimetinib & Encorafenib Exploratory Trials EST. INDICATION DRUG(S) PHASE 1 PHASE 1B PHASE 2 PHASE 3 PATIENT Bini + Encor ± LEE011 (CDK 4/6) BRAF V600+ melanoma 179 Selected tumors Bini and Encor as single agents <100 LOGIC-2 BRAF V600+ melanoma Bini + Encor plus third agent* 140 Encor + Cetuximab ± BYL719 BRAF+ mCRC 150 (PI3K α ) BRAF+ mCRC <100 Encor + Cetux. + WNT974 BRAF V600+ melanoma Encor + LEE011 (CDK 4/6) <100 BRAF V600+ tumors Encorafenib single agent <100 Binimetinib + BYL719 (PI3K α ) RAS or BRAF+ solid tumors <100 NRAS melanoma Binimetinib + LEE011 (CDK 4/6) <100 Mutant or wild-type RAS mCRC <100 Binimetinib + Panitumumab Uveal Melanoma Binimetinib + Protein kin. C <100 Solid tumors Binimetinib + Ganitumab <100 Binimetinib + Encorafenib Ovarian cancer <100 Binimetinib + Paclitaxel Encorafenib Solid tumors Bini + BKM120 (pan-PI3K) <100 Binimetinib *Third agent: LEE011 (CDK 4/6 inhibitor), pan FGFR inhibitor, BKM120 (pan PI3K inhibitor) or 13 c-MET inhibitor Investigator-sponsored trials and clinical pharmacology studies not listed above
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