NKTR-214 Demonstrates Improved Efficacy in Resistant Preclinical Melanoma Model Through Preferential Activation of Tumor Killing Immune Cell Subtype

SAN FRANCISCO, CA, USA I April 7, 2013 I Nektar Therapeutics (NKTR) today presented positive preclinical data for NKTR-214, a novel cancer immunotherapy which targets the IL-2 receptor complex, at the 2013 American Association for Cancer Research (AACR) Annual Meeting. NKTR-214 is a new immunocytokine that is being developed as a potential treatment for multiple cancers.  NKTR-214 targets the IL-2 receptor complex through selective receptor binding to the IL2Rβ subtype.  Activation of the IL2Rβ subtype promotes tumor killing by the body’s own immune system.

“We are extremely encouraged by the dramatic efficacy observed with NKTR-214 treatment in an aggressive and resistant preclinical model of melanoma,” said Stephen Doberstein, Ph.D., Senior Vice President and Chief Scientific Officer of Nektar Therapeutics.  “NKTR-214 is specifically designed to harness the potent immunostimulatory effects of the IL-2 receptor complex while minimizing the immunosuppressive effects that have greatly limited the efficacy of the native IL-2 protein.  Importantly, NKTR-214 represents the first application of our technology platform to target a receptor subtype in the tumor microenvironment while avoiding the unwanted effects from off-target receptor binding.  NKTR-214 also has improved pharmacokinetics and enhanced tumor penetration which allow for a ten-fold reduction in overall dosing.  We are excited about the potential of NKTR-214 to emerge as a powerful new immunotherapy in the fight against cancer.”

NKTR-214 is a novel immunocytokine therapy that is engineered using Nektar’s polymer conjugate technology to selectively target the beneficial IL-2 receptor complex.  In the preclinical data presented at AACR, NKTR-214 exhibits differentiated IL-2 receptor binding which results in significantly altered immune cell populations in the tumor microenvironment compared to the clinically validated IL-2 protein therapy, aldesleukin.  Specifically, NKTR-214 maintains high affinity for the IL-2 receptor subunit beta, which activates tumor-killing T cells within the tumor microenvironment.  At the same time, NKTR-214 exhibits up to 100-fold reduced affinity to the IL-2 receptor subunit alpha-beta, which activates immuno-suppressive regulatory T-cells.  In a well-validated animal model of melanoma, NKTR-214 demonstrated significantly improved dosing, at once every 9 days as compared to twice a day dosing with aldesleukin.

The data was presented today at the AACR Annual Meeting 2013 in Poster Session, Immunology 2, (Abstract #482): Charych, et al., “Tipping the balance in the tumor microenvironment: An engineered cytokine (NKTR-214) with altered IL-2 receptor binding selectivity and improved efficacy in a mouse melanoma model.”  

About Nektar 
Nektar Therapeutics is a biopharmaceutical company developing novel therapeutics based on its PEGylation and advanced polymer conjugation technology platforms. Nektar has a robust R&D pipeline of potentially high-value therapeutics in pain, oncology and other therapeutic areas.  In the area of pain, Nektar has an exclusive worldwide license agreement with AstraZeneca for naloxegol (NKTR-118), an investigational drug candidate, which has completed Phase 3 clinical development as a once- daily, oral tablet for the treatment of opioid-induced constipation.  This agreement also includes NKTR-119, an earlier stage development program that is a co-formulation of naloxegol and an opioid. In the proprietary pipeline, NKTR-181, a novel mu-opioid analgesic candidate for chronic pain conditions, is in Phase 2 development in osteoarthritis patients with chronic knee pain.  NKTR-192, a novel mu-opioid analgesic in development to treat acute pain is in Phase 1 clinical development.  In oncology, etirinotecan pegol (NKTR-102) is being evaluated in a Phase 3 clinical study (the BEACON study) for the treatment of metastatic breast cancer and is also in Phase 2 studies for the treatment of ovarian and colorectal cancers. 

Nektar’s technology has enabled eight approved products in the U.S. or Europe through partnerships with leading biopharmaceutical companies, including UCB’s Cimzia® for Crohn’s disease and rheumatoid arthritis, Roche’s PEGASYS® for hepatitis C and Amgen’s Neulasta® for neutropenia. Additional development-stage products that leverage Nektar’s proprietary technology platform include Baxter’s BAX 855, a long-acting PEGylated rFVIII program, which is in Phase 3 clinical development.

Nektar is headquartered in San Francisco, California, with additional operations in Huntsville, Alabama and Hyderabad, India.  Further information about the company and its drug development programs and capabilities may be found online at http://www.nektar.com.

SOURCE: Nektar Therapeutics