NKTR-102 (PEG-Irinotecan) Demonstrates Significant Anti-Tumor Activity and Improved Pharmacokinetic Profile in Preclinical Studies Presented at ECCO
BARCELONA, Spain, September 27, 2007 /PRNewswire-FirstCall/ -- Nektar Therapeutics announced positive new preclinical data today regarding its proprietary product candidate, NKTR-102 (PEG-irinotecan), which is under development for the treatment of solid tumors. NKTR-102 is a PEGylated form of irinotecan created using Nektar's innovative small molecule PEGylation technology platform. The data were presented today at the 14th Annual European Cancer Conference (ECCO 14).
"These preclinical data are encouraging and warrant continued evaluation of NKTR-102 in human trials," said Dan Von Hoff, M.D., F.A.C.P., Clinical Professor of Medicine at University of Arizona's Department of Medicine and Director of the Clinical Translational Research Division at the Translational Genomics Research Institute in Arizona. "The results show that NKTR-102 demonstrated statistically significant dose-related suppression of tumor growth in an irinotecan-resistant mouse xenograft model. Further, NKTR-102 displays extended and unique pharmacokinetics which results in greater and sustained exposure to both irinotecan and its active metabolite."
NKTR-102 substantially suppressed tumor growth in an irinotecan-resistant mouse colorectal tumor model, while irinotecan-treated groups did not show a statistically significant decrease in tumor growth compared to controls. The studies also demonstrate that administration of NKTR-102 results in a significantly improved pharmacokinetic profile for the active metabolite of irinotecan as compared to treatment with irinotecan.
"These studies highlight the ability of Nektar's small molecule PEGylation technology to serve as a powerful platform for improving chemotherapeutic agents, "said Hoyoung Huh, M.D., Ph.D. Chief Operating Officer and Head of the PEGylation Business Unit. "Based on our progress with the current Phase 1 trial underway for NKTR-102, we anticipate advancing this key program into Phase 2 clinical development by year-end."
Preclinical Data for NKTR-102
Preclinical studies in an irinotecan-resistant mouse colorectal tumor model evaluated comparative anti-tumor activity and pharmacokinetics of NKTR-102 and irinotecan. A single IV administration of NKTR-102 on days 0, 4 and 8 in tumor-bearing mice resulted in substantially suppressed tumor growth in a statistically significant dose-related manner. NKTR-102 inhibited tumor growth by 94% at the highest dose of 90 mg/kg on day 50. In addition, tumor regression was observed with NKTR-102 at the same dose level. There was no significant decrease in tumor growth and no tumor regression from equivalent doses of irinotecan.
NKTR-102 administration demonstrated greater and sustained systemic exposure to irinotecan and its active metabolite as compared to irinotecan at equivalent doses. In a rat model, administration of NKTR-102 resulted in an 80-fold increase in systemic exposure (plasma AUC) of the active metabolite of irinotecan and an 11-fold increase in half-life (40 hours versus 3.5 hours). In a mouse model, NKTR-102 administration resulted in a 90-fold increase in the tumor half-life of the active metabolite of irinotecan (15 days versus 4 hours) and an over 300-fold increase in its tumor exposure (AUC).
The preclinical studies also showed that NKTR-102 was well-tolerated.
Preclinical Data Presentations for NKTR-102
The two poster presentations made today at the 14th Annual European Cancer Conference (ECCO) can be found on Nektar's website at http://www.nektar.com/wt/page/nktr102_media :
P-0722: "Anti-tumor activity and pharmacokinetics of NKTR-102, a novel PEGylated-irinotecan conjugate, in irinotecan-resistant colorectal tumors implanted in mice"
P-0727: "NKTR-102, a novel PEGylated-irinotecan conjugate, demonstrates improved pharmacokinetics with sustained exposure of irinotecan and its active metabolite"
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 Phase 1 clinical development. 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.
Nektar PEGylation Platform
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 Roche's PEGASYS(R) for hepatitis C and Amgen's Neulasta(R) for neutropenia.
Nektar Therapeutics is a biopharmaceutical company that develops and enables differentiated therapeutics with its industry-leading PEGylation and pulmonary drug development technology platforms. Nektar PEGylation and pulmonary technology, expertise, manufacturing capabilities have enabled nine approved products for partners, which include the world's leading pharmaceutical and biotechnology companies. Nektar also develops its own products by applying its PEGylation and pulmonary technology platforms to existing medicines with the objective to enhance performance, such as improving efficacy, safety and compliance.
This press release contains forward-looking statements regarding the potential of the company's PEGylation technology platform and NKTR-102. These forward-looking statements involve important risks and uncertainties, including but not limited to: (i) preclinical testing and clinical trials for NKTR-102 are long, expensive and uncertain processes, (ii) because the NKTR-102 product development programs are in the early phases of clinical development, the risk of failure is high and can occur at any stage of development, (iii) the company may fail to obtain regulatory approval of NKTR-102, (iv) potential competition from approved drugs or drugs under development that may be safe and effective for the same indication as that targeted by NKTR-102, and (v) the company's patent applications for NKTR-102 may fail to issue; patents that have issued may not be enforceable; or unanticipated intellectual property licenses from third parties may be required in the future. Other important risks and uncertainties are detailed in the company's reports and other filings with the SEC including its most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q. Actual results could differ materially from the forward-looking statements contained in this press release. The company undertakes no obligation to update forward-looking statements, whether as a result of new information, future events, or otherwise. No information regarding or presented at the scientific meetings referred to above (or contained at the Internet links provided) is intended to be incorporated by reference in this press release.
Contacts: Tim Warner (650) 283-4915 or Stephan Herrera (415) 488-7699 or Jennifer Ruddock (650) 631-4954 firstname.lastname@example.org email@example.com firstname.lastname@example.org
CONTACT: Tim Warner, +1-650-283-4915, , or StephanHerrera, +1-415-488-7699, , or Jennifer Ruddock,+1-650-631-4954, , all of Nektar Therapeutics email@example.com firstname.lastname@example.org email@example.com
Web site: http://www.nektar.com/
Ticker Symbol: (NASDAQ-NMS:NKTR)
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Posted: September 2007