Nektar Therapeutics (NKTR)

[surf1944]

Nektar Announces Expanded Phase 2 Clinical Development Plan For NKTR-102 (PEG-irinotecan)
Monday June 2, 8:31 am ET
Phase 2 Study for NKTR-102 Will Target Newly-Identified K-Ras Mutated Oncogene Population in Patients with Advanced Colorectal Cancer
New Phase 2 Clinical Trials Will Evaluate NKTR-102 in Advanced Breast and Ovarian Cancers

SAN CARLOS, Calif., June 2 /PRNewswire-FirstCall/ -- Nektar Therapeutics (Nasdaq: NKTR - News) today announced an expanded Phase 2 development plan for NKTR-102 (PEG-irinotecan). The company will target newly-characterized colorectal cancer patients with K-Ras mutated gene status in its Phase 2 study in advanced colorectal cancer. In addition, NKTR-102 will be evaluated in Phase 2 trials in two new indications: platinum-refractory ovarian cancer and advanced breast cancer that is refractory to anthracycline and/or taxane-based therapies. These studies are expected to commence in the second half of 2008.

Recent data(2) presented at the 2008 American Society of Clinical Oncologists (ASCO) Annual Meeting shows colorectal cancer (CRC) patients with tumors that have K-Ras oncogene mutations (K-Ras mutant types) do not respond to EGFR-inhibitors, such as cetuximab. It is estimated that up to 45% of colorectal cancer cases have this mutated K-Ras gene. To target this newly- characterized K-Ras mutant patient population, Nektar will initiate a prospective study to evaluate the efficacy of NKTR-102 monotherapy in these patients. The primary endpoint of this randomized trial will be a clinically meaningful improvement in progression-free survival as compared to standard irinotecan monotherapy.

"With these recent clinical studies on K-Ras, there is no longer a clear standard of care for the second-line treatment of advanced colorectal cancer in patients with the K-Ras gene mutation," said Daniel Haller, M.D., Professor of Medicine at the Abramson Cancer Center at the University of Pennsylvania. "This novel oncolytic, NKTR-102, could offer an alternative and promising approach for tumors in this patient population."

The company also announced new trials for NKTR-102 in breast and ovarian cancer. These studies will be open-label, single-arm studies to evaluate the overall response rate (ORR) of NKTR-102 monotherapy in each tumor setting. The studies will implement a minimax design, known as the Simon design, which was first proposed by Dr. Richard Simon of the National Cancer Institute in 1989. The two-stage design is routinely used in the evaluation of oncolytics.(1)

"The promise of NKTR-102 and our small molecule PEGylation platform is capturing a great deal of attention among oncologists and clinical investigators," said Howard W. Robin, Nektar President and CEO. "We've seen significant and repeat anti-tumor activity in our Phase 1 study with NKTR-102. Our expanded Phase 2 clinical development plan will potentially accelerate our understanding and development of this novel therapy in multiple cancer types."

Details on the NKTR-102 Phase 2 clinical development plan will be discussed at an event on June 2, 2008 at 6:30 PM Central time. The event will be Webcast and can be accessed from the company's website at the following url: http://www.nektar.com/wt/page/asco.

About NKTR-102 (PEG-irinotecan)

Nektar is developing NKTR-102, a PEGylated form of irinotecan, which was invented by Nektar using its world-leading small molecule PEGylation technology platform. The product is currently in a Phase 2a study to evaluate NKTR-102 in combination with cetuximab.

Irinotecan is an important chemotherapeutic agent used for the treatment of solid tumors, including colorectal and lung cancers. By applying Nektar's small molecule PEGylation technology to irinotecan, NKTR-102 may prove to be a more powerful and tolerable anti-tumor agent. Preclinical studies show that treatment with NKTR-102 results in significant suppression of tumor growth in an irinotecan-resistant mouse colorectal tumor model and in similar models of breast and lung cancer. Administration of NKTR-102 in an animal model also results in a markedly improved time-concentration profile for SN38, the active metabolite of irinotecan, as compared to treatment with irinotecan.

Nektar PEGylation technology can enhance the properties of therapeutic agents by increasing drug circulation time in the bloodstream, decreasing immunogenicity and dosing frequency, increasing bioavailability and improving drug solubility and stability. It can also be used to modify pharmaceutical agents to preferentially target certain systems within the body. It is a technique in which non-toxic polyethylene glycol (PEG) polymers are attached to therapeutic agents, and it is applicable to most major drug classes, including proteins, peptides, antibody fragments, small molecules, and other drugs. Nektar PEGylation technology is also used in eight additional approved partnered products in the U.S. or Europe today, including UCB's Cimzia® for Crohn's Disease, Roche's PEGASYS® for hepatitis C and Amgen's Neulasta® for neutropenia.