On February 24, 2014 Synta reported on progress with lead compounds from its Hsp90-Inhibitor Drug Conjugate (HDC) platform at the IASLC 14th Annual Targeted Therapies of the Treatment of Lung Cancer Meeting in Santa Monica, California (Press release Synta Pharmaceuticals, FEB 24, 2014, View Source [SID:1234500122]). The new compounds, consisting of an Hsp90-inhibitor conjugated with SN-38 (HDC SN-38) and an Hsp90-inhibitor conjugated with docetaxel (HDC docetaxel), demonstrated proof of principle in multiple preclinical cancer models. Notably, complete or near complete regressions of tumors were observed in models of non-small cell lung cancer, small-cell lung cancer, breast cancer, pancreatic cancer, colon cancer, and skin cancer, in models that are generally resistant or show limited response to treatment with the unconjugated chemotherapies.
Results presented at the conference showed that up to seven times greater dosage of docetaxel may be safely administered in the animal models compared to unconjugated docetaxel. This increase was associated with near complete regressions in animals treated with the HDC vs. limited activity or progressive disease in animals treated with unconjugated docetaxel. Preclinical safety results to date show comparable or more favorable safety profile of the HDC as compared with the unconjugated chemotherapy.
In addition, both the SN-38 and docetaxel HDCs demonstrated prolonged anti-tumor activity following the last dose of the HDC. These results are consistent with retention of the HDC in tumors and sustained, slow release of the cytotoxic payload within the tumor.
Slides presented at the IASLC meeting are available here View Source .