Enabling the repurposing of niclosamide for castrate-resistant prostate cancer using a novel formulation technology platform

Prostate cancer is the most common diagnosed cancer developing in men, developing in around 160,000 men in the United States. While many men are successfully treated of the disease, nearly 30,000 continue to die each year to do an advanced cancer which continues to grow despite castration levels of androgen present. A new generation of androgen receptor signal inhibitors has come to the market and successfully improved the survival of patients. However, resistance to the new agents is inevitable and occurs in the first few years after beginning treatment. The resistance has been shown to be linked to splice variants in the androgen receptor. Niclosamide has recently been discovered to inhibit at least splice variant expression AR-V7, which in combination with next generation androgen receptor signal inhibitors has shown a synergistic effect. In a recent phase I feasibility study however, niclosamide failed as a therapeutic due to bioavailability limitations. Niclosamide is poorly water-soluble drugs who would benefit from our formulation design and processing technology platform which improves upon current amorphous solid dispersions, the technique currently used in 19 FDA approved products. Preliminary evidence presence promising results for improvements in the drugs bioavailability with this formulation technique. We propose to optimize the formulation through a quality by design approach to maximize the performance of the drug in the formulation platform. After validating the performance of niclosamide with our formulation platform with a pharmacokinetic study we will perform an efficacy study in a subcutaneous xenograft mouse model of castration-resistant prostate cancer to support the efficacy of the drug in feasible doses for future clinical testing.If successful the proposed research would contribute to the development of a new treatment for patients with castration-resistant prostate cancer, improving the progression free survival in these patients.