1. Lenalidomide Nonclinical Overview Dr. David Stirling Chief Scientific Officer Celgene Corporation

2. Lenalidomide Nonclinical Pharmacokinetic Studies • Rapidly absorbed • Extensive distribution into tissues • Low protein binding • Does not inhibit or induce major cytochrome P450 isozymes • Partial metabolism related to hydrolysis observed in vivo • Rapidly excreted via the urine mainly as unchanged drug

3. Lenalidomide vs Thalidomide • Lenalidomide and thalidomide are pharmacologically different drugs based on • Chemistry/metabolism • Structurally linked • No common breakdown products • Cellular biology • Significant potency differences • Molecular biology • Del 5q sensitivity • Clinical profile • Different safety profiles • Non-clinical reproductive/development toxicology • Lenalidomide is not selectively toxic to development • Lenalidomide did not produce limb malformations

4. Reproductive and Developmental ToxicityAdditional Studies in Rabbits • Pulse dosing study completed • High dose on GDs 8 through 10 • No malformations • Additional Seg II studies in progress • Dose-ranging study with TK completed • Developmental toxicity study completed • Analysis and report preparation underway

5. Lenalidomide: Cellular Mechanism • Anti-proliferative (proapoptotic, cell cycle arrest) • Proerythropoietic (stimulate HbF synthesis) • Cytokine regulation (TNFα, IL-10, IL-2, IFN-γ) • Immune stimulation (T cells, NK cells) • Anti-angiogenic • Expand progenitor cell populations