Results of a Randomized Study of the JAK Inhibitor Ruxolitinib (INC424) versus Best Available Therapy (BAT) in Primary Myelofibrosis (PMF), Post- Polycythemia.

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Results of a Randomized Study of the JAK Inhibitor Ruxolitinib (INC424) versus Best Available Therapy (BAT) in Primary Myelofibrosis (PMF), Post- Polycythemia Vera-Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia-Myelofibrosis (PET-MF) Harrison CN et al. Proc ASCO 2011;Abstract LBA6501.

COMFORT-II: Phase III Trial of JAK1/JAK2 Inhibitor Ruxolitinib versus BAT Harrison CN et al. Proc ASCO 2011;Abstract LBA6501. Patients with PMF, PPV-MF, or PET-MF with ≥2 IPSS risk factors N = 219 Randomize 2:1 Best available therapy (BAT) n = 73 Ruxolitinib crossover and extension phase Randomized, open-label, multicenter Phase III trial Patients were stratified based on baseline IPSS risk category Progression events that qualified for the crossover and extension phase: –Splenectomy –Progressive splenomegaly as defined by a 25% increase in spleen volume compared with the on-study nadir (including baseline) INC424 (ruxolitinib) 15 or 20 mg oral BID n = 146

Patients with ≥35% Decrease in Spleen Volume at Weeks 24 and 48 With permission from Harrison CN et al. Proc ASCO 2011;Abstract LBA6501. Median time to response = weeks Of patients (n = 69) who achieved ≥35% reduction in spleen volume at any time during the study, 64% (n = 44) did so at the first assessment (at 12 weeks) RuxolitinibBATRuxolitinibBAT Ruxolitinib p < BAT % n = 41 Ruxolitinib p < BAT % n = 46 Primary EndpointKey Secondary Endpoint % with ≥35% spleen volume reduction Week 48Week 24

Percent Change in Spleen Volume from Baseline With permission from Harrison CN et al. Proc ASCO 2011;Abstract LBA Ruxolitinib p < RuxolitinibBAT Primary endpoint % change from baseline at week 48 RuxolitinibBAT Spleen volume 132 (97%)35 (56%) Spleen volume 4 (3%)28 (44%) Best response at any time on study

Duration of Spleen Volume Reduction With permission from Harrison CN et al. Proc ASCO 2011;Abstract LBA6501. Patients achieving ≥35% spleen volume reduction at any time on study: 47.9% Median duration of reduction was not reached: 79.7% of patients still responding * Event: <35% reduction from baseline and ≥25% increase from nadir Event* Probability Weeks from onset Censored Observed events, n (%): 14 (20.3) Censored events, n (%): 55 (79.7)

Change in EORTC QLQ-C30 Scores at Week 48 Compared to Baseline With permission from Harrison CN et al. Proc ASCO 2011;Abstract LBA6501. Improvements were seen by week eight and continued through week Ruxolitinib Mean change from baseline Global health status/QoLRole functioning n = BAT Worsening Improvement

Additional Secondary Endpoints Ruxolitinib (n = 146) BAT (n = 73) Hazard ratiop-value Progression-free survival 70%74% Leukemia-free survival 96%95% Overall survival96%95% Harrison CN et al. Proc ASCO 2011;Abstract LBA6501.

Hematology Laboratory Values (Worst Lab Grade on Study * † ) Harrison CN et al. Proc ASCO 2011;Abstract LBA6501. Grade 1 (%) Grade 2 (%) Grade 3 (%) Grade 4 (%) Hemoglobin Ruxolitinib (n = 146) BAT (n = 70) Platelet count Ruxolitinib (n = 146) BAT (n = 69)16643 The majority of patients (63% ruxolitinib, 67% BAT) had Grade 1 or 2 anemia at baseline. In both arms, all patients who entered the study had ≤Grade 1 thrombocytopenia at baseline. * Occuring on the randomized treatment phase only † Percentage is based on baseline total n

Select Nonhematologic Adverse Events Ruxolitinib (n = 146) BAT (n = 73) Any gradeGrade 3 or 4Any gradeGrade 3 or 4 Diarrhea23%1%11%0% Peripheral edema22%0%26%0% Asthenia16%1%10%1% Dyspnea16%1%18%4% Nasopharyngitis15%0%14%0% Pyrexia14%2%10%0% Nausea13%1%7%0% Arthralgia12%1%7%0% Cough13%0%15%1% Fatigue12%1%8%0% Harrison CN et al. Proc ASCO 2011;Abstract LBA6501.

Conclusions The study met its primary and key secondary endpoints with statistical significance. Ruxolitinib demonstrated significant and sustained improvement in splenomegaly, disease-related symptoms, functioning and quality of life. BAT-treated patients experienced progressive splenomegaly and either no change or worsening of symptoms. The safety profile of ruxolitinib was acceptable relative to the control. The data extend the positive results of the COMFORT-I trial, which compared ruxolitinib to placebo. Data from the COMFORT studies indicate that ruxolitinib has the potential to significantly improve the current treatment landscape for most patients with MF.