A Quantitative Multi-Gene RT-PCR Assay for Prediction of Recurrence in Stage II Colon Cancer (CC): Selection of the Genes in 4 Large Studies and Results of the Independent, Prospectively-Designed QUASAR Validation Study Kerr D et al. ASCO 2009; Abstract (Oral Presentation)

Study Goals Develop and validate a multi-gene expression assay that improves treatment decisions for patients with stage II colon cancer, and… –provides individualized assessment of recurrence risk following surgery –identifies patients with differential 5FU/LV benefit –provides clinical value in the context of other measures such as T-stage and MMR/MSI –is optimized for fixed, paraffin-embedded colon tumor tissue

Colon Cancer Technical Feasibility Selection of Final Gene List & Algorithm Clinical Validation Study: Stage II Colon Cancer QUASAR (n=1,436) Test Prognosis and Treatment Benefit Assay Development and Validation Standardization and Validation of Analytical Methods Development Studies Surgery Alone NSABP C-01/C-02 (n=270) Cleveland Clinic (n=765) Development Studies Surgery + 5FU/LV NSABP C-04 (n=308) NSABP C-06 (n=508)

Modeling and Analytical Performance 48 Recurrence and 66 Treatment Benefit Genes Significant Across Development Studies Assessment of 761 Candidate Genes in 1,851 Patients in the Development Studies to Yield Final Pre-specified Assay for Validation in QUASAR RECURRENCE SCORE ® (0-100) TREATMENT SCORE (0-100) 7 Recurrence Genes6 Treatment Benefit Genes5 Reference Genes FINAL ASSAY

Parent QUASAR study n=3,239 Patients with collected blocks n=2,197 (68%) Confirmed stage II colon cancer n=1,490 (69%) Final evaluable population n=1,436 (711 surgery alone, 725 surgery + chemo) 54 excluded (3.6%): 29 synchronous tumors 8 insufficient tissue 7 identifier queries 6 RNA quality/quantity 4 ineligible histology 707 cases stage III and rectal cancer QUASAR: Evaluable Stage II Colon Cancer Patients

Is there a significant relationship between the risk of recurrence and the pre-specified continuous Recurrence Score in patients with stage II colon cancer randomly assigned to surgery alone? STROMAL FAP INHBA BGN CELL CYCLE Ki-67 C-MYC MYBL2 REFERENCE ATP5E GPX1 PGK1 UBB VDAC2 GADD45B RECURRENCE SCORE Calculated from Tumor Gene Expression QUASAR: Pre-Specified Primary Endpoint — Recurrence Risk

5040 QUASAR Results: Continuous RS Predicts Recurrence in Stage II CC (N = 711) Following Surgery Source: With permission from Kerr D et al. ASCO 2009; Abstract year recurrence rate Recurrence Score p = % 5% 10% 15% 20% 25% 30% 35%

Kaplan-Meier Estimates (95% CI) of Recurrence Risk at 3 years QUASAR Results: Recurrence Risk in Pre-Specified Recurrence Risk Groups (n = 711) Source: With permission from Kerr D et al. ASCO 2009; Abstract Recurrence Risk Group Range of RS Proportion of patients Low<3043.7% Intermediate % High≥4125.6% 22% (16%-29%) 18% (13%-24%) 12% (9% -16%) Years Recurrence Risk Group High Intermediate Low Proportion Event Free

Results: Clinical/Pathologic Covariates and Recurrence Source: Kerr D et al. ASCO 2009; Abstract Variable CategoriesHRP value MMR13% deficient vs 87% proficient0.32<0.001 T stage15% T4 vs 85% T Tumor grade29% High vs 71% Low No. nodes examined62% LVI13% Present vs 87% Absent RS per 25 unitsContinuous Prespecified Multivariate Analysis: Patients Who Underwent Surgery Alone (n=605)

RS, T Stage and MMR Deficiency: Key Independent Predictors of Recurrence in Stage II CC Source: With permission from Kerr D et al. ASCO 2009; Abstract % 5% 10% 15% 20% 25% 30% 35% 40% 45% Recurrence Score 3-year recurrence rate MMR deficient (11% of Stage II patients) T4 stage (13% of Stage II patients) T3 and MMR proficient (76% of Stage II patients)

Treatment Score Prediction of 5FU/LV Benefit Treatment Score by treatment interaction was not significant for RFS (p = 0.19), DFS (p = 0.12) or OS (p = 0.15) "The proportional benefits of chemotherapy were maintained across the recurrence score prognostic categories. Therefore if you had a high chance of the tumor recurring as predicted by the Recurrence Score, the absolute benefits of chemotherapy would be somewhat higher.” Source: Kerr D et al. ASCO 2009; Abstract Editor: Overall, QUASAR demonstrated that chemo resulted in fewer recurrences — HR = 0.78 ( ; p = 0.001)* *Lancet 2007; 370: Editor: Overall, QUASAR demonstrated that chemo resulted in fewer recurrences — HR = 0.78 ( ; p = 0.001)* *Lancet 2007; 370:

Source: Kerr D et al. ASCO 2009; Abstract Key Conclusions First demonstration that a prospectively-defined gene expression assay can independently predict recurrence in stage II CC following surgery –Recurrence Score (RS) provides independent value beyond available prognostic factors RS provides individualized assessment of recurrence risk –Greatest clinical utility when used in conjunction with T stage and Mismatch Repair (MMR/MSI), particularly for the majority of patients for whom those markers are uninformative (~70% of patients) The continuous Treatment Score (TS) did not predict a differential benefit from 5FU/LV