The Slamon/Mak cancer stem cell drug discovery program funded by CIRM/CSCC has achieved two important milestones in the past year. Our first therapeutic candidate was approved by the FDA and first-in-human dosing of CFI-400945 has taken place as part of the Phase I clinical trial. In our second program we have selected a development candidate that is now in the midst of IND ennabling studies
The clinical trial is being carried out at Princess Margaret Cancer Centre (Principal Investigator, Dr Philippe Bedard) and UCLA (Principal Investigator, Dr Zev Wainberg). This clinical trial was initiated after a number of milestones were successfully met following the submission of the IND and CTA in 2013. These have included making improvements to the formulation of the CFI-400945 tablets resulting in the successful reduction of the appearance of a degradant that was slowly accumulating in the initial formulation. This enabled the manufacturing of the cGMP tablets for use in the clinic in September 2013. These formulation changes and the Certificates of Analysis of these tablets were submitted to the FDA and permission was granted to begin clinical evaluation. In December 2013, we were awarded the CIRM Disease Team III funding to continue the CFI-400945 program which enabled the planning and initiation of this Phase I clinical evaluation and additional non-clinical studies.
In our second program, Pyrazolo-pyrimidines have emerged as the most promising class of 3rd series TTK inhibitors. TTKis with potent in vitro activity, excellent oral exposure in rats and in vivo efficacy were identified. A short list of 5 pyrazolo-pyrimidines was identified as potential third series development candidates. After further characterization it was determined that 4 or 5 compounds met the preponderance of the selection criteria, 2 of which had outstanding PK properties. The TTK inhibitor CFI-402257 had the best balance of efficacy, PK and off-target activities and was selected as the development candidate. IND enabling studies with 402257 have been initiated, and will continue during the no cost extension period of the grant.