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Lenalidomide Nonclinical Overview

Lenalidomide Nonclinical Overview. Dr. David Stirling Chief Scientific Officer Celgene Corporation. Lenalidomide Nonclinical Pharmacokinetic Studies. Rapidly absorbed Extensive distribution into tissues Low protein binding Does not inhibit or induce major cytochrome P450 isozymes

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Lenalidomide Nonclinical Overview

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  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

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