The repeated dose toxicity studies are the principal studies that support the safety profile of a new drug. As such, the FDA require two-species repeated dose toxicity studies prior to filing an IND in anticipation of a Phase 1 clinical trial. The key highlights of the studies that supported the development of the Company's protocol for Phase 1 were as follows:
- COTI-2 was able to achieve a No Observed Adverse Effect Level ("NOAEL") determined in both a rodent and non-rodent species using an oral dosing regimen that was both well tolerated at and above levels that have been effective in recent xenograft experiments. This allows for the selection of a starting oral dose in the Phase 1 clinical trial within the dosing parameters established from the toxicity studies;
- The studies were conducted with a five day on and two day off dosing schedule repeated for a total of 28 days in both species. Achieving an NOAEL for this dosing regimen provides a treatment regime of Monday to Friday dosing with weekends off, which is generally well tolerated from a patient's perspective; and,
- The range of apparently safe and effective doses for COTI-2 was identified as being quite wide for a cancer drug and is consistent with COTI-2 having a good safety profile.
"The results of these crucial experiments have confirmed the low toxicity of COTI-2 observed during preclinical development. This important positive data will be shared with potential licensing partners who have been waiting on these results and the data have been incorporated into our IND document targeted for filing by the end of the year." - Dr. Wayne Danter.