ANX-514 is a novel, detergent-free reformulation of the chemotherapy drug docetaxel. Taxotere®, a branded formulation of docetaxel, is approved to treat breast, non-small cell lung, prostate, gastric and head and neck cancers.

Background and Potential Benefits

Taxotere has several limitations; principally, toxicity associated with its excipient, polysorbate 80. Taxotere has been associated with acute hypersensitivity reactions, ranging widely in incidence and severity, and has also been associated with fluid retention. Many patients suffer severe (in rare cases, fatal) hypersensitivity reactions immediately following Taxotere administration. The occurrence of hypersensitivity reactions has been attributed, in part, to the intrinsic toxic effects of polysorbate 80; more specifically, to its oxidation products, which are known to cause histamine release. Even following premedication with corticosteriods, which is required for Taxotere therapy, hypersensitivity reactions have been observed, including, in rare cases, fatal anaphylaxis.

ANX-514 was designed to have clinically comparable release of docetaxel relative to Taxotere while eliminating the presence of polysorbate 80 and ethanol, both of which are used to solubilize docetaxel in the Taxotere formulation. The ANX-514 formulation solubilizes docetaxel using oil droplets comprised of a combination of non-toxic excipients. Docetaxel is contained within these oil droplets and can be administered intravenously without using detergents as pharmaceutical vehicles. Once in central circulation, the emulsion is metabolized rapidly, leaving chemically-identical active ingredient to exert its cytotoxic effect. The rate and extent of absorption of docetaxel from ANX-514 was designed to be comparable to that of Taxotere, resulting in similar clinical outcomes attributable to the active ingredient.

As a detergent free formulation of docetaxel, we believe ANX-514 has the potential to improve the tolerability and safety of docetaxel treatment while eliminating toxicities associated with the presence of the polysorbate 80 detergent in Taxotere and complications associated with the Taxotere premedication regimen. ANX-514 may reduce the incidence and severity of hypersensitivity reactions and delay the onset of fluid retention. ANX-514 also may minimize other adverse reactions to polysorbate 80, such as neurotoxicity.

In addition, the high-dose corticosteroid premedication required for treatment with Taxotere may be unnecessary with detergent-free ANX-514. We believe that eliminating the high-dose corticosteroid premedication required for treatment with Taxotere would represent a significant benefit to cancer patients, particularly those who have diabetes or a predisposition to hyperglycemia, who we estimate constitute one-third of the patients who receive Taxotere. Corticosteroids expose cancer patients to otherwise unnecessary and costly complications, such as hyperglycemia, immunosuppression and insomnia.

Development Status

In October 2011, we met with the FDA to discuss our clinical development plans for ANX-514 and the FDA agreed that our proposed non-inferiority study (Study 514-02) with a primary objective of comparing fluid retention following treatment with ANX-514, administered without corticosteroid premedication, and Taxotere, administered with corticosteroid premedication would generate sufficient clinical data to support approval of ANX-514 without requiring corticosteroid premedication. We plan to initiate this study in 2012.

About Study 514-02

Study 514-02 will be a randomized, open-label, multicenter, non-inferiority study comparing ANX-514, administered without corticosteroid premedication, and Taxotere, administered with corticosteroid premedication in accordance with its label, in the treatment of non-small cell lung cancer after failure of prior platinum-based therapy. Approximately 400 patients will be enrolled and treated until evidence of progressive disease, unacceptable toxicity, withdrawal of consent, or other withdrawal criteria are met.

The primary objective of Study 514-02 will be to compare the incidence of fluid retention between study arms. The secondary objectives will be to compare ANX-514 and Taxotere in terms of overall safety profile, objective response rate, duration of response, progression-free survival and overall survival.