Nektar Therapeutics (Nasdaq: NKTR) presented promising data today from preclinical studies of NKTR-181, a next-generation mu-opioid analgesic candidate with a novel molecular design. NKTR-181 is being developed to effectively treat pain while addressing the abuse liability and serious side effects associated with traditional opioid therapies. The data are being featured in an oral abstract session and poster presentation today at the 5th Annual Frontiers of Clinical Investigation Symposium – Pain 2010: From Bench to Bedside in La Jolla, CA.
NKTR-181 was uniquely designed to cross the blood-brain barrier at a substantially slower rate than other opioid therapies. With a reduced rate of entry into the CNS, NKTR-181 has the potential to eliminate not only the euphoria that underlies opioid abuse liability and dependence, but also the serious CNS-related side effects of respiratory depression and sedation. The unique molecular design of the polymer drug conjugate also prevents conversion of NKTR-181 into a rapid-acting abusable form of an opioid. NKTR-181 is currently in IND-enabling studies and Nektar plans to begin Phase 1 clinical studies in the first part of 2011.
"Opioid analgesics represent the gold standard in pain control but they pose significant safety risks, and their misuse and abuse have been cited as serious public health issues. NKTR-181 is the first mu-opioid analgesic with a novel molecular structure specifically engineered to eliminate the euphoric high and dangerous side effects associated with this class of painkillers," said Stephen K. Doberstein, Ph.D., Senior Vice President and Chief Scientific Officer of Nektar Therapeutics. "In highly-predictive preclinical models of analgesia and abuse liability, NKTR-181 has shown comparable analgesia to oxycodone with minimal CNS side effects and as a result, we are enthusiastic about the potential of this new therapeutic to dramatically advance the field of pain management."
NKTR-181 Data Highlights from Pain 2010
Data presented includes receptor binding and function studies that demonstrate NKTR-181 binds specifically to the mu-opioid receptor and acts as a full agonist. In standard preclinical models of pain, NKTR-181 demonstrated full suppression of pain symptoms comparable to oxycodone. NKTR-181 also displayed slowed kinetics of entry to the brain in vivo as compared to oxycodone, with a 90% reduction in the rate of entry into the brain versus oxycodone. The slower rate of brain-uptake correlated with dramatically diminished abuse liability and CNS side effects. At analgesic doses, NKTR-181 displayed no significant CNS side effects and in a self-administration model of abuse liability, NKTR-181 displayed no reinforcing properties up to the highest dose tested.
The oral and poster presentations from the Pain 2010 meeting can be found on Nektar’s website at www.nektar.com:
- Fishburn et. al., “NKTR-181: A Novel Opioid With Slowed Brain Entry Shows Low Abuse Liability and Reduced CNS Side Effects”
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