P2X₃ and P2X_2/3 Antagonist Program

• Pain and urinary incontinence
• Potential first-in-class molecule
• Industry has struggled to find drug-like molecules
• Planning Phase I in 2009

First- and Best-in-Class Opportunity

The P2X₃ and P2X_2/3 receptors are also members of the P2X purinergic receptor family of ligand-gated ion channels. Evotec believe that the P2X₃ and P2X_2/3 receptors are promising therapeutic targets for major medical needs in the areas of chronic pain and bladder dysfunction. These receptors are present in a restricted subset of primary sensory neurons which transmit pain signals, and preclinical studies examining their function suggest that they may have important roles in pain signaling and bladder function in humans.

Studies conducted using small molecule antagonists of P2X₃ and P2X_2/3 as well as gene knockdown experiments, have demonstrated profound pain relief in multiple preclinical models of chronic inflammatory and neuropathic pain as well as urinary incontinence. Because the industry has struggled to design or identify drug-like ligands that inhibit these receptors, Evotec believes it has an opportunity for a first- and best-in-class drug therapy.

Evotec have identified proprietary small molecule antagonists of P2X₃ and P2X_2/3 and are actively engaged in optimizing drug-like leads to support the selection of a candidate for IND-enabling studies. Clinical development of a first-in-class P2X₃ antagonist drug candidate are due to commence in 2009.