Ann: Successful MPSVI Safety Review and PARA OA 008 Update, page-80

I'm not expecting consistent, positive trends for any of the structural biomarkers at day 53, including COMP, but I won't be surprised if we do see changes at day 53. I do however expect consistent, positive trends at 6 months. This is mostly because of the amount of time it will take for the narrowing of the joint space to be stabilised and/or improved, since we are dealing with a process that involves cell turnover, changes to systemic processes, particularly those in the synovium, all of which take time.

BML reduction by day 53 may lead to a reduction in these biomarkers, but the variability normally associated with the measurement of biomarkers may obscure any positive trend. For example, if you compare biomarkers for a single individual at different times of the day you will probably get different quantities at each time point. The composition of synovial fluid also rarely stays the same since it is a combination of filtrate from the blood as well as secretions from the surrounding synovium. The synovium can also differ in viscosity. Taken together, these natural variables could significantly increase the error bars and potentially rule out a significant change. For the graph that you showed, do you know if they performed a significance test or is there any indication of the size of the error bars? Instead, it may be possible that we may not see a consistent positive trend until the 6 month time point when these structural biomarkers are consistently low.

Anyway, I don't think we can read too much into the biomarkers at such an early time point, but I do think the more significant readout (irregardless of the outcome this week) is at the 6 month point. Lets just hope there is no trading halt on Friday, owing to the long weekend.