The filing of your IND has been delayed a number of times since the early fall of 2014. What is causing the delays in filing your IND application with the FDA for COTI-2?
Since the latter part of January, we have revised our target for filing the IND to the end of the first quarter of 2015 and we wish to assure you that we are on track to achieve that goal. That being said, as noted in your question, we are several months behind our original schedule for filing this important application, and there have been two main unanticipated issues that have caused this delay.
The first issue arose when we scaled up our GMP (good manufacturing practices) chemistry to produce the kilogram quantities of COTI-2 required for the Phase I material to be given to patients. When scaled up, the original standard preparation route, which worked well for the small quantities used in our preclinical studies, produced impurities that were unacceptable. A new synthetic route had to be found which took time to develop. Our new method for preparing the COTI-2 is very clean with very low levels of any contaminants and is actually much cleaner than with our original small quantity method. Although this issue was resolved, it did result in an approximately three month delay.
The second issue arose more recently when we were finalizing the COTI-2 oral suspension to be given to patients. We made a slight adjustment to the suspending material in order to improve its taste and thus patient compliance. While we were advised that this should not produce any issues, the formulation change did result in a degradation of COTI-2 over time in this suspension material that was deemed unacceptable in maximizing patient outcomes. We were forced to return to our original formulation of COTI-2 in a commonly used suspension, OraPlus. This change has resulted in good stability and purity over time. This final chemistry issue is resolved but resulted in a further delay of two months.
The IND is now in the final writing of the chemistry section and formatting of the document. In spite of the delays, we have consistently avoided rushing the process in order to assure that the highest quality document will be submitted and thus improve the timing of approval with the FDA. To be clear, we are on track for an IND submission by the end of the first quarter of 2015.
I would also like to add that we are planning on filing a Health Canada CTA once the IND has been filed in the U.S., and we are very close to finalizing a very experienced and prestigious Scientific Advisory Board to guide and consult on the clinical development of COTI-2 in multiple cancer indications.