Nektar Presents Positive Preclinical Data On Oral, Peripherally-Acting Kappa Agonist Molecules At 2014 American Academy Of Pain Management Meeting

Nektar Therapeutics

today announced results from preclinical studies characterizing the analgesic profiles of a series of the company's internally-discovered oral, peripherally-acting kappa opioid receptor agonist molecules. The preclinical research candidates were created using Nektar's small molecule polymer medicinal chemistry platform. The analgesic properties of kappa receptor agonism are well described in the medical literature.1,2 Kappa opioid receptors are expressed in the peripheral nervous system as well as in the central nervous system (CNS), and activation of these receptors at both sites has been shown to result in a reduction in pain and inflammation in a wide range of preclinical models.1,4 However, the therapeutic use of kappa receptor agonists has been limited because activation of these receptors in the CNS is associated with significant dysphoria and other unwanted side effects (i.e., anxiety, restlessness and fidgeting).3 "We are encouraged by the results of our research, which shows that we can achieve efficacy through the peripheral activation of the kappa opioid receptor, while at the same time reducing the side effects observed with centrally-acting kappa agonist molecules," said Stephen K. Doberstein, Ph.D., senior vice president and chief scientific officer of Nektar Therapeutics. "With this research, we are continuing to capitalize on the ability of our small molecule polymer medicinal chemistry platform to create new peripherally-acting molecules that could address different pain conditions." Results presented showed that a series of novel, oral, peripherally-acting kappa agonist molecules demonstrated a 15-fold improved therapeutic index (separation between efficacy and CNS-mediated side effects) compared with kappa agonist molecules that were not peripherally selective. The preclinical data is being presented today at the American Academy of Pain Management Annual Meeting (Choi IY, et al. Characterization of novel, oral peripherally-acting kappa agonists in preclinical models).