NKTR-102 Demonstrates Anti-Tumor Activity And Improved Pharmacokinetic Profile

Armen Hareyan's picture

Nektar Therapeuticsannounced positive new preclinical data 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.

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"

About NKTR-102

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 for hepatitis C and Amgen's Neulasta(R) for neutropenia.