The multiple ascending dose study is the second study in the Phase 1 clinical program for NKTR-181. Positive results from the first Phase 1 study, which was a single ascending dose trial in 110 healthy subjects, were presented at the American Academy of Pain Management (AAPM) Annual Meeting in September 2011.NKTR-181 is currently being prepared for Phase 2 development in chronic pain patients in mid-2012. About NKTR-181 NKTR-181 is a novel mu-opioid analgesic investigational drug candidate created using Nektar's advanced small molecule polymer conjugate technology. The unique molecular design of the polymer conjugate is designed to prevent conversion of NKTR-181 into a more abusable form of an opioid. With slower entry into the CNS when compared to published oxycodone data, NKTR-181 has the potential to greatly reduce the euphoria that underlies opioid abuse liability and dependence. In addition, NKTR-181 is intended to reduce the other serious CNS-related side effects such as respiratory depression and sedation which are associated with current opioid therapies. About Opioids and Pain Management Pain is the most common symptom for which patients seek medical attention.(1) According to the American Pain Society, the prevalence of chronic pain in the United States is estimated to be 35.5% or 105 million people. 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 direct health-care expenditures and lost work time.(1) Opioids are considered to be the most effective therapeutic option for pain and have over $10 billion a year in sales in the U.S. alone.(2,3) However, opioids cause significant problems for physicians and patients because of their serious side effects such as respiratory depression and sedation, as well as the risks they pose for addiction, abuse, misuse, and diversion. The U.S. Food and Drug Administration has cited prescription opioid analgesics as being at the center of a major public health crisis of addiction, misuse, abuse, overdose and death.(4) A 2010 recent report from the Center for Disease Control and Prevention (CDC) notes that emergency room visits tied to the abuse of prescription painkillers is at an all-time high, having increased 111 percent over a five-year period.(5) About Nektar Nektar Therapeutics is a biopharmaceutical company developing novel therapeutics based on its PEGylation and advanced polymer conjugation technology platforms. Nektar's technology and drug development expertise have enabled seven approved products in the U.S. or Europe for leading biopharmaceutical company partners, including UCB's Cimzia(R) for Crohn's disease and rheumatoid arthritis, Roche's PEGASYS(R) for hepatitis C and Amgen's Neulasta(R) for neutropenia. Nektar has created a robust pipeline of potentially high-value therapeutics to address unmet medical needs by leveraging and expanding its technology platforms to improve and enable molecules. In addition to the releasable polymer technology, Nektar is the first company to create a permanent small molecule-polymer conjugate with enhanced oral bioavailability and restricted entry into the CNS. Nektar is currently conducting clinical and preclinical programs in oncology, pain and other therapeutic areas. Nektar has an exclusive worldwide license agreement with AstraZeneca for its oral NKTR-118 program to treat opioid-induced constipation and its NKTR-119 program for the treatment of pain without constipation side effects. NKTR-102 is being evaluated in Phase 2 clinical studies for the treatment of ovarian, breast and colorectal cancers.