APH-0912 is a combination of a Taxotere® prodrug and monoclonal antibody targeted to treat metastatic cancer

The prodrug is a combination of a docetaxel molecule, the potent anticancer drug, and a sugar molecule to enhance solubility covalently linked to a tumor-specific antibody. This molecular combination is not bioactive prior to administration.

After infusion and adsorption onto targeted cancer cells facilitated by the cancer-specific monoclonal antibody, serum enzymes will break down the prodrug into the bioactive docetaxel and a sugar molecule.

Taxotere® Prodrugs

Taxotere® prodrugs are covalently bound to tumor-specific antibodies with improved water solubility achieved by utilizing sugars as hydrophilic appendages to docetaxel. Since taxoids are susceptible to Lewis acids often utilized in glycosylation protocols, sugars are tethered to the C-10 hydroxyl group in a taxoid through an ester linkage.

In Vitro Efficacy of Taxotere® Prodrugs

The in vitro antitumor activities of the various Taxotere® prodrugs were examined using P-388 leukemia cells. All docetaxel prodrug derivatives, with the exception of the most water-soluble derivative 10-α-MAG-DT, were more active than docetaxel in a dose-dependent manner.

In Vivo Efficacy of Taxotere® Prodrugs

The in vivo antitumor activities of the docetaxel prodrugs versus paclitaxel and controls were also tested. Again, all docetaxel prodrug derivatives, with the exception of the most water-soluble derivative 10-α-MAG-DT, were more active than paclitaxel in the constant dose in vivo studies.

The effects of 10-α-GAG-DT and docetaxel on body weight (side effect) were evaluated. Interestingly, at a dosing level of 20 mg/Kg, the decrease in body weight as an index of side effects is suppressed for the prodrug 10-α-GAG-DT compared to docetaxel. Research results suggest that these docetaxel derivatives act as prodrugs without the use of a toxic solvent, and for the most part are superior to paclitaxel in terms of both in vitro and in vivo bioactivities and equivalent to docetaxel in therapeutic efficacy.

APH-0912 – Targeted Taxoid Prodrug with Monoclonal Antibody

APH-0912 will be preferably administered intravenously for metastatic cancer patients so that the non-localized cancers can be targeted and treated by the anti-mitotic agent, docetaxel after being released by sera enzymes.

We are utilizing patented phospholipid nanosomes to enhance the residence time and bioavailability of this targeted Taxotere® prodrug, APH-0912.