K777 is a cysteine protease inhibitor discovered through the collaboration between CDIPD (then the NIH-sponsored Tropical Disease Research Unit) and Khepri Biosciences (later Celera). Over the succeeding decade, K777 moved through the drug development pipeline with support from the National Institutes of Allergy and Infectious Diseases, The Sandler Foundation, and the Institute for OneWorld Health. It is now undergoing late-stage preclinical development according to recommendations from a successful pre-IND meeting with the FDA. Aside from its original activity against Trypanosoma cruzi, the causative agent for Chagas' disease, K777 has also shown activity in animal models of hookworm infection, schistosomiasis and cryptosporidiosis, and inhibits the molting of Onchocerca volvulus, the causative agent of river blindness.
CDIPD member, Dr. Anjan Debnath, developed the first high-throughput screen for identifying drugs effective against Entamoeba histolytica. While screening a library of FDA-approved drugs and bioactives, Dr. Debnath discovered auranofin as an FDA-approved drug with better efficacy than the current treatment for amebiasis. This drug, originally developed for rheumatoid arthritis, has received Orphan Drug Status from the FDA, and is also effective against Giardia, Trichomonas, Cryptosporidium, Onchocerca and Brugia. For more details see recent press releases and publications.
A collaboration with Anacor led to the identification of a potent lead series effective against trypanosomes in culture, as well as in an animal model of acute infection. CDIPD Director, James McKerrow, introduced Anacor to DNDi to facilitate further development of this series. With synthetic chemistry and PK support from Scynexis, a lead compound has been developed into a clinical candidate, oxaborole SCYX-7158. This drug candidate is now in clinical trials and was declared "Project of the Year 2011" by DNDi.
Corifungin, a natural product discovered and produced by Acea Pharmaceuticals, was shown by CDIPD investigators Dr. Geraldine DeMuylder and Dr. Anjan Debnath to have efficacy against Naegleria fowleri, the causative agents of primary amoebic meningal encephalitis, and Leishmania donovani, the parasite responsible for visceral leishmaniasis. CDIPD is collaborating with the Acea Pharmaceuticals to seek funding from NIAID for preclinical testing. Corifungin has received Orphan Drug Status from the FDA.