nPT-mTOR

A series of unique mTOR inhibitors for a variety of indications.

Programme background
Biotica’s nPT-mTOR programme is a series of novel rapamycin analogues created using novoPT™. In an early lead compound, the major site of CYP3A4 metabolism was removed, resulting in improved PK compared to the parent. Compounds in the bPT-mTOR series have shown good activity in a range of inflammatory disease models and in xenograft models of cancer, including orthotopic glioblastoma models.

Potential utility in inflammatory disorders and cancer
mTOR is the target of rapamycin, a drug which is clinically used as an immunosuppressant to prevent transplant rejection. The target has more recently been clinically validated in a range of inflammatory disorders. In addition to its immunomodulatory effects, mTOR is also important in cell proliferation and angiogenesis, and the semi-synthetic rapamycin analogues temsirolimus and everolimus are approved for the treatment of renal cell carcinoma.

Partnership with Wyeth
In October 2006, Biotica implemented a partnership agreement with Wyeth for the bPT-mTOR programme. The research and license agreement included a licence to Biotica’s library of rapamycin analogues, a research collaboration and the right to develop and commercialise resulting drug candidates. The programme offered numerous benefits:

• The novoPT™ technology enabled creation of compounds that are impractical to make using traditional medicinal chemistry
• The lead compound had greater metabolic stability and improved PK properties compared with rapamycin
• The lead compound was shown to be active in a variety of animal disease models
• The partnership exploited Wyeth’s rich clinical and preclinical expertise with rapalogs