May 29 - June 2, 2015 TIGER-X: Rociletinib Activity in EGFR T790M Mutant NSCLC CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

clinicaloptions.com/oncology TIGER-X: Rociletinib Activity in EGFR T790M Mutant NSCLC TIGER-X: Rociletinib (CO-1686) in Advanced NSCLC  Rociletinib: third-generation oral, irreversible EGFR-TKI –Inhibits EGFR with activating mutations and T790M while sparing WT –Received FDA breakthrough therapy designation in May 2014  TIGER-X: phase I/II trial of rociletinib safety and efficacy in advanced EGFR mutation–positive NSCLC with acquired EGFR-TKI resistance –Previous results demonstrated activity in pts with or without T790M mutation –Current report focused on efficacy based on EGFR mutation analysis by genotyping plasma vs tumor tissue Sequist LV, et al. ASCO Abstract Sequist LV, et al. N Engl J Med. 2015;372:

clinicaloptions.com/oncology TIGER-X: Rociletinib Activity in EGFR T790M Mutant NSCLC TIGER-X: Rociletinib in Previously Treated EGFR Mutation-Positive NSCLC Rociletinib 500 mg BID (n = 119) EGFR mutation– positive previously treated advanced or recurrent NSCLC with acquired resistance to prior EGFR TKI (N = 456) Key outcomes: safety and tolerability, PK profile, ORR Sequist LV, et al. ASCO Abstract Rociletinib 625 mg BID (n = 236) Rociletinib 750 mg BID (n = 95) Phase II expansion cohorts  Upon progression on EGFR TKI  T790M+ biopsy at entry  Stable CNS metastases ok Phase I dose escalation Rociletinib BID 21-day cycles escalate to MTD

clinicaloptions.com/oncology TIGER-X: Rociletinib Activity in EGFR T790M Mutant NSCLC TIGER-X: Pt Population Characteristic 500 mg (n = 119) 625 mg (n = 236) 750 mg (n = 95) 1000 mg (n = 6) Total (N = 456) Female, % Median age, yrs Enrolled in US, % ECOG PS 0, % Median prior treatment, %  1 prior TKI  > 1 prior TKI  Immediate prior TKI History of CNS disease, % Sequist LV, et al. ASCO Abstract 8001.

clinicaloptions.com/oncology TIGER-X: Rociletinib Activity in EGFR T790M Mutant NSCLC TIGER-X: Tumor Response Across Rociletinib Dosing Sequist LV, et al. ASCO Abstract Reprinted with permission SLD Change From Baseline (%) 500 mg BID HBr 625 mg BID HBr 750 mg BID HBr 1000 mg BID HBr Ongoing 500 mg625 mg750 mg1000 mgTotal N ORR (%) DCR (%) Individual Patients

clinicaloptions.com/oncology TIGER-X: Rociletinib Activity in EGFR T790M Mutant NSCLC TIGER-X: Safety Across Rociletinib Dosing  Improved safety profile with 500 mg BID vs higher doses –Grade 3 QTc prolongation 2.5% –Discontinuation due to treatment-related AEs 2.5% vs 4% overall  Once recognized, hyperglycemia manageable with oral agents AE (All Grades), % 500 mg (n = 119) 625 mg (n = 236) 750 mg (n = 95) 1000 mg (n = 6) Hyperglycemia  Grade 3/ Diarrhea Nausea QTc prolongation Sequist LV, et al. ASCO Abstract 8001.

clinicaloptions.com/oncology TIGER-X: Rociletinib Activity in EGFR T790M Mutant NSCLC TIGER-X: Plasma Testing for EGFR Mutations  Plasma EGFR mutation assessed via digital PCR/flow cytometry assay shows good sensitivity and specificity vs standard tissue testing –81% agreement for T790M and 87% for activating mutations –Identified several T790M+ samples missed by tissue testing –T790M status confirmed in subsequent tissue testing –Plasma-based test overcomes limitations of tissue specimen availability  Similar ORR in samples identified as T790M+ with plasma vs tissue –53% (78/147) vs 53% (85/160)  Rociletinib also active in subset of pts confirmed T790M WT –ORR: 32% to 39% Sequist LV, et al. ASCO Abstract 8001.

clinicaloptions.com/oncology TIGER-X: Rociletinib Activity in EGFR T790M Mutant NSCLC TIGER-X: Conclusions  Rociletinib active and well tolerated in EGFR mutation–positive advanced NSCLC pts who have progressed after prior TKI therapy [1] –Recommended dose 500 mg BID due to lower toxicity vs higher doses –ORR 60%, disease control rate 90% at this dose  T790M testing using plasma-based assay may provide viable alternative to tumor biopsy [1] –Authors suggest plasma assay may better reflect disease heterogeneity  Additional TIGER trials under way to further explore rociletinib activity in EGFR-mutant NSCLC [2-4] 1. Sequist LV, et al. ASCO Abstract ClinicalTrials.gov. NCT ClinicalTrials.gov. NCT ClinicalTrials.gov. NCT

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