After going over the primary endpoint and statistical analysis...

After going over the primary endpoint and statistical analysis plan again, it seems we should only expect to see changes in some biomarkers at Day 56, but for others not until the 6-month mark. Some are fast acting, whereas others require more time to change.

For example, the inflammatory biomarkers IL-1b, TNF-a and IL-6 should drop in the treated group by Day 56.

CTX-I, CTX-II, ADAMTS-5, TIMP-1, COMP and C2C are all structural biomarkers, so we may not see changes until the 6-month point, and we may not see any significant changes at day 56. It seems the value of these biomarkers is showing that they correlate with changes seen in MRI images.

One to keep an eye out for is NGF, since this could generate a lot of value for PAR if found to be reduced by day 56 and at 6 months. It will also demonstrate the MOA that iPPS acts through to treat pain.

So we have three mechanisms that will demonstrated for iPPS: 1) anti-inflammatory, 2) DMOAD and / or 3) NGF inhibitor.