1. Phase I/II Trial of the MEK1/2 Inhibitor GSK1120212 (GSK212) in Patients with Relapsed/ Refractory Myeloid Malignancies: Evidence of Activity in Pts with RAS Mutation Borthakur G et al. Proc ASCO 2011;Abstract 6506.

2. Borthakur G et al. Proc ASCO 2011;Abstract 6506. Background –Signaling through the RAS/RAF/MEK pathway is activated in many human cancers. –GSK212 is a potent, selective allosteric inhibitor of MEK1/2 that inhibits proliferation of myeloid cell lines in vitro. –A Phase I/II study of a single, daily, oral dosing regimen was conducted. Study Objectives: –Define the recommended Phase II dose (RP2D) of GSK212. –Evaluate pharmacokinetics, toxicity and preliminary activity in patients with previously treated hematologic malignancies.

3. Phase I/II Study Design Eligibility Relapsed/refractory AML, poor-risk MDS (>5% blasts), ALL, CMML ECOG PS 0-2 Adequate organ function Borthakur G et al. Proc ASCO 2011;Abstract 6506. ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CMML, chronic myelomonocytic leukemia; MDS, myelodysplatic syndrome Recommended Phase II dose = 2 mg QD 3 mg loading 1 mg QD n = 3 1 mg QD n = 2 2 mg QD n = 9 Cohort 1 RAS-mutant AML MDS Cohort 2 RAS wild type or unknown Cohort 3 RAS-mutant CMML RP2D 3 + 3 dose escalation Phase 1 Dose escalationPhase 2 Expansion

4. Patient Characteristics: 2 mg/Day Dose Characteristic n = 47 Median age, years (range)64 (21-87) Number of prior therapies, median2 ECOG PS, n (%) 0-1 2 34 (72) 13 (28) Diagnosis, n (%) AML Other 42 (89) 5 (11) RAS mutation, n (%)16 (34) FLT3 mutation, n (%)18 (38) Cytogenetics, n (%) Complex Core-binding factor Normal Other/unknown 9 (19) 2 (4) 8 (17) 17 (37) Borthakur G et al. Proc ASCO 2011;Abstract 6506.

5. Clinical Activity Best Response, n (%) N or KRAS Mutated (n = 16) RAS Wild Type or Unknown (n = 31) CR/CRp3 (19)0 MLFS1 (6)0 Partial response01 (3) HI/HI-N/HI-P1 (6)5 (16) Stable disease10 (63)8 (26) Progressive disease013 (42) Overall response rate4 (25)1 (3) Borthakur G et al. Proc ASCO 2011;Abstract 6506. MLFS = morphologic leukemic-free state ORR = CR/CRp/MLFS/PR 6 patients not evaluable

6. Select Adverse Events* AEs (N = 47) All GradesGrade 3/4 Diarrhea47%4% Pyrexia30%6% Rash26%4% Fatigue25%4% AST increase24%11% ALT increase23%11% Pneumonia23%17% Febrile neutropenia23%19% Borthakur G et al. Proc ASCO 2011;Abstract 6506. * Occurring in greater than 20% of patients

7. Events of Special Interest Borthakur G et al. Proc ASCO 2011;Abstract 6506. Decrease in LVEF –Six percent (3/47) of patients had drug-related left ventricular dysfunction (1 Grade 1 event and 2 Grade 2 events). Transaminase elevations –Two patients had drug held due to transaminase elevations on rechallenge, 1 positive and 1 negative. Ocular toxicity –Central Serous Retinopathy: Fluid accumulation in the macular region between retinal pigment epithelium and out segment. –One patient developed a reversible retinopathy.

8. Borthakur G et al. Proc ASCO 2011;Abstract 6506. Author Conclusions Acceptable safety profile: –Monotherapy safety profile suggests potential to combine with other antileukemic therapies Preliminary efficacy: –Overall response rates of 25 percent (4 of 16) among patients with RAS mutation Enrolling patients with RAS-mutant AML, MDS and CMML: –Centralized RAS mutation analysis –Up to 30 sites in US and Europe open to accrual