"The data from this study reinforce our belief that NKTR-181 could potentially transform the treatment of chronic pain," said Robert Medve, MD, Chief Medical Officer at Nektar Therapeutics. "Unique to this new mu-opioid analgesic molecule is that it does not rely on a formulation to decrease its abuse liability. With a ten-fold slower entry into the brain as compared to oxycodone, NKTR-181 avoids the rush into the brain associated with euphoria. Adding to our excitement is the data that shows the peripheral analgesic and anti-hyperalgesic effects of NKTR-181 in multiple pain models. We will seek to capitalize on the properties of this unique molecule as we advance NKTR-181 into Phase 2 development this year."In a separate presentation of preclinical data at the AAPM Meeting, NKTR-181 resulted in less sedation and abuse liability as compared to oxycodone in multiple animal models across a wide range of doses. As predicted from its molecular design, NKTR-181 has a reduced rate of entry into the brain in rodents. This feature contributed to a 30-fold shift in the dose-response for abuse liability and a 10-fold shift in the dose response for sedation relative to oxycodone. Chronic pain conditions, such as osteoarthritis, back pain and cancer pain, affect at least 126 million adults in the U.S. annually and contribute to over $100 billion a year in lost productivity.(2) About the NKTR-181 Phase 1 Multiple Ascending Dose Study This Phase 1, double-blind, randomized, placebo-controlled, ascending multiple dose study of NKTR-181 was conducted in the U.S. at Lifetree Clinical Research. The study enrolled a total of 60 healthy subjects over an eight-day treatment period. Four dose cohorts were evaluated with 15 subjects in each dose cohort (100 mg, 200 mg, 300 mg, 400 mg). Subjects in each cohort received oral twice-daily doses of NKTR-181 (n=12) in aqueous solution or placebo (n=3) following an overnight fast. Pharmacokinetics were determined through serial blood samples. Serial opioid pharmacodynamic tests included the cold-pressor test (CPT) and a UVB injury model to assess both centrally-mediated and peripherally-mediated analgesic effects. A pupillometry test was used as an indicator of the onset of opioid effect. Statistical analyses are based on a repeated-measure mixed model analysis of variance.