Positive preclinical data was presented by Nektar Therapeutics lead oncolytic candidate, NKTR-102 (PEG-irinotecan), which demonstrated enhanced anti-tumor activity in a mouse xenograft model of colorectal cancer when co-administered with bevacizumab. Presented at the American Association for Cancer Research (AACR) Annual Meeting 2008 in San Diego, California, the data also featured the enhanced pharmacokinetic profile and tolerability of NKTR-102, as compared to irinotecan in animal models.

NKTR-102 is a PEGylated form of irinotecan developed using Nektar's innovative small molecule PEGylation technology platform. NKTR-102 is currently in a Phase 2 development program to evaluate its safety and efficacy as a second-line colorectal cancer therapy in combination with cetuximab. Nektar had previously announced its intention to expand the NKTR-102 Phase 2 clinical development program later this year with additional indications.

NKTR-102 also exhibited superior pharmacokinetics in a repeated dose study in dogs, with a 6-fold increase in exposure (AUC) and a 4-fold lower peak plasma concentration (Cmax) of SN38, the active metabolite of irinotecan, as compared to the equivalent dosing of irinotecan. The lower peak plasma concentration of NKTR-102 was associated with a superior tolerability profile, with less gastrointestinal and hematopoietic toxicity than comparable doses of irinotecan.

In the preclinical studies presented at AACR, NKTR-102 was co-administered with bevacizumab to evaluate the effects of combination therapy. The combination therapy had an additive effect, inhibiting tumor growth by up to 97% in an irinotecan-resistant mouse xenograft model of colorectal cancer (HT29), which was greater than monotherapy with either NKTR-102 or bevacizumab. NKTR-102 at 46 mg/kg, co-administered with bevacizumab, also resulted in eight partial tumor regressions and one complete tumor regression. This compares to no tumor regressions observed with bevacizumab monotherapy, and two partial regressions and one complete regression with NKTR-102 monotherapy. NKTR-102 alone, and in combination with bevacizumab, was well-tolerated, with minimal weight loss.

In animal models, NKTR-102 had a markedly improved safety and tolerability profile when compared to irinotecan in animal models. Both the incidence and severity of diarrhea and neutropenia were lower in dogs treated with NKTR-102 as compared to irinotecan. Diarrhea and neutropenia are the most common side effects associated with irinotecan treatment, and can limit treatment with the therapy.