1. Phase I Study of PLX4032: Proof of Concept for V600E BRAF Mutation as a Therapeutic Target in Human Cancer Flaherty K et al. American Society of Clinical Oncology 2009; Abstract 9000. (Clinical Science Symposium Presentation)

2. Source: Flaherty K et al. ASCO 2009; Abstract 9000. Introduction V600E BRAF kinase activating mutation –Point mutation that constitutively activates map-kinase pathway –Observed in 6-8% of all cancers, including melanoma (60%) colorectal cancer (10%), anaplastic and papillary thyroid carcinomas, low-grade serous ovarian carcinomas Phase I, sequential dose-escalation study of PLX4032 (oral agent — the most selective BRAF inhibitor to have entered clinical development — N = 55: 49 melanoma, 3 thyroid, 1 rectal, 1 ovarian, 1 germ cell)

3. 100 75 50 25 0 -25 -50 -75 -100 Patients (n = 15)* (RECIST cutoff for PR, 30%) Source: With permission from Flaherty K et al. ASCO 2009; Abstract 9000. Results Patients with BRAF V600E Melanoma Treated with PLX4032 > 240 mg BID * One patient with M1c had 55% reduction in target lesions, but PD in non-target lesions; died before end C2 (not included above) % change from baseline (sum of lesion size)

4. Source: With permission from Flaherty K et al. ASCO 2009; Abstract 9000. Results Patient with BRAF V600E Melanoma PET Scan at Baseline and Day +15 Treatment at 320 mg BID A patient with response in extensive “intransit” metastases on the leg and more distant skin and lymph node sites

5. Source: Flaherty K et al. ASCO 2009; Abstract 9000. Summary and Conclusions Nearly all AEs were mild and transient, mostly rash, fatigue, photosensitivity but also cutaneous squamous cell cancer following chronic dosing (n = 6) Responses to PLX4032 with V600E+ melanoma –9 PRs in 15 patients –Regression of liver, lung and bone metastases –Symptom improvement in many patients –Premature to define PFS, but it appears to be ~6 months, with many patients still on therapy –No evidence of tumor regression in 5 patients with V600E- negative disease 3 patients with V600E+ papillary thyroid carcinoma: 1 PR, 2 SD Additional trials planned in melanoma, colorectal cancer and papillary thyroid carcinoma