A great series of posts
@Mozzarc - thanks for all your work on this.
Really interesting stuff about the concentration of different biomarkers in different fluids. Where it is created and what the reductions may be in the SF given we have shown an 11.9% reduction in COMP in serum from P2. My gut feel is that the reductions may be greater in the SF. But I do wonder what the definition of 'passing' the primary endpoint really is (the ANZCTR just says "Change from baseline at day 56 in one or more synovial fluid biomarkers") Its hard to imagine how we could possibly not pass the primary endpoint given the very broad and generic definition of it (and the data we've seen in P2, we will almost certainly see a reduction in at least COMP and ADAMTS). Beyond that though - what would the definition of "DMOAD" be? This will be important for interpreting the results and their significance.
Incredible stuff though this 008. The whole depth and breadth of this small quick study is really hitting home as there are so many benefits of its results to Paradigm.
It gives us the opportunity to show DMOAD, which increases the value of the treatment and the uptake (having a multiplicative effect on the value of the asset). It also gives a look-through to the P3 primary endpoint being Womac pain after 56 days against placebo. We have Koos pain against placebo, and we have Womac pain (no placebo) from recent SAS, but for the first time ever will have Womac against placebo which will "give us the results before the test" for P3! With every step we are thinking of the following two steps! 008 also gives us a whole lot of biomarker data which may be useful for many things beyond even the milestone of DMOAD (I'm thinking a few extra endpoints in 006 like blood/urine biomarkers)
Really interesting to ponder the usefulness of biomarker data. The possibility of identifying/treating at-risk patients or those in the very early stages of the disease. It helps avoid unnecessary degradation to a point where the pain increases to a moderate/severe level (whereas it may be prevented at a low level of severity or prior to chronic disease). This increases our potential market in the process.
Extrapolating backwards in time even further - given the recent success of stockmarket darlings Rhythm(RHY) and Bard1(BD1) and the emergence of biomarker assaying and AI for early detection of disease (in their cases various cancers), perhaps we can build a significant proprietary database over time and develop an algorithm to detect and even quantify/categorise OA. While not as life threatening as cancer, early detection (before symptoms) and treatment may result in much better outcomes over the long term. RHY started with up to 60 blood biomarkers and have gotten it down to 1 primary and 4 adjunct biomarkers and now have a simple blood test that is more accurate than the FIT (poo) test for screening colorectal cancer. These diagnostic companies are worth $250-$300M with no revenue (with upside on MC when commercialised), and no method to treat the disease - just identifying risk. Diagnostics can be a big business, and the beauty of us identifying OA early would be that we can also offer the solution! A nice symbiotic business line. Just dreaming aloud.
(20min delay)