he 008 program was always going to be a fascinating one. Yes the n was very very small...just 17 to 20 odd patients in each of the three cohorts...but the data? Oh the data....and it's ramifications...let's take a quick look tonight in regards to this program, at what we have and just what might be to come?
As per usual, please enjoy.
THE SPLITS
No no no not these splits...I mean the splitting up of data, the slicing and dicing. If I did this my legs would snap off..I'm about as flexible as an old steel pipe.
The way 008 was split, made it a unique study for a number of reasons, a number of specific divisions and splices of the observables:
1) Three groups, placebo, once weekly and twice weekly
2) Data gathering split into four distinct parts :
A) Wet Biomarkers B) Structural observables C) Womac observations D) PGIC and Rescue
3) Not only that, but we as holders were very fortunate to also get three distinct TIME point splits:
i) 56 day ii) 128 day iii) One year
The results to date have been quite outstanding, not only in an absolute number sense, but also in a statistical sense. To achieve some parameters coming through at a statistical sense in such low numbers is quite simply exemplarily.
RECAP THE DISEASE
So here is a diagrammatic image of the damage and how it manifests in and around the joint 1:
This data that PAR are presenting has simply never been seen before in a durational human study...ever.
The natural regression of BML's for example is slow if it actually occurs with any therapies... not everyone's BML's regress! The data here is showing us there is a meaningfully more rapid reversal of BML's in the iPPS cohort.
BML link to progression of OA?
Oh you better believe it...here is a quote from one of the world's top OA researchers on the planet, Dr David Felson:
"Twenty-seven of 75 knees with medial lesions (36.0%) showed medial progression versus 12 of 148 knees without lesions (8.1%) (odds ratio for progression, 6.5 [95% CI, 3.0 to 14.0]). Approximately 69% of knees that progressed medially had medial lesions, and lateral lesions conferred a marked risk for lateral progression. These increased risks were attenuated by 37% to 53% after adjustment for limb alignment". 2
But it's the conclusion of this research that has the link for us:
"Bone marrow edema is a potent risk factor for structural deterioration in knee osteoarthritis... ".
The link between BMLs and joint replacement is also clear, this quote from another group of researchers3 published in 2010:
"The prevalence and severity of BMLs are associated with less tibial cartilage volume and greater cartilage loss over 2 years. Moreover, severity of BMLs was positively associated with risk of knee joint replacement over 4 years. This provides further support for the importance of BMLs in identifying those with OA most likely to progress. Identifying factors that prevent or reduce the severity of BMLs may provide an important target in the prevention of disease progression and treatment of OA, and the subsequent need for arthroplasty".
What was the odds ratio for the above?
"The risk of knee joint replacement over 4 years increased with increasing BML score (odds ratio 1.57; 95% CI 1.04, 2.35; P=0.03)".
(Mozz speak for odds ratio 1.57, you have a 57% greater chance of needing a knee joint replacement compared to not needing one with increased BMLs).
As a reminder in preparation for the upcoming results either this week or next week....I give you PAR's own observations from 005. 4
We need to show a few things here to demonstrate a regression of BMEL's....the first is the overall volume...
"At day 53 compared to baseline, there was a strong trend for the iPPS group having greater reduction in total BML Volume [-34.2% vs. -3.6%]".
Ah yes good Mozz, but what about area?
"...total BML maximal area [-25.3% vs. +11.9%] compared with the placebo group".
So wait, Placebo further disintegrated by 11.9% and yet iPPS caused a reversal of some 25.3% ?
Yep.
Yeah that's great Mozz but can you show us any good results in the Medial chamber, that's where most of the load bearing aspect of the joint is...Can you show me that against placebo?
Sure.
"Effects of iPPS were noted in the medial compartment of the knee for BML volume [-37.0% vs. +2.2%] "
What about area??
Of course...
"BML area compared with the placebo group [-22.9% vs. +6.8%] ".
Have you guys noticed in the last three statements, placebo continued to degenerate, but what did the iPPS group do? Reverse.
Indeed achieving good results in the medial compartment is very important as the "prevalence of knee osteoarthritis in the medial compartment is 4-times of the prevalence in the lateral compartment".
You show regression here, you are actually addressing this disease from a disease modification aspect.
Par reported it to us back in Early 2019.
"iPPS group was more likely to have BML regression compared with the placebo group in the medial compartment (50.0% vs. 27.3%, p=0.03), and total knee (51.9% vs. 37.7%)".
Yes I agree with you reading this, it would be really a cherry on the top if we saw an example of this in the form of a pic with an actual PAR patient from 005...
Will we see some more MRI pics one day? Might have to wait for Peer review but it's one I'm looking forward to!
Guys, I ask you, what is to come in the next few days....what will be the update to his amazing data that we see from the 6 month full quantitative data?
Excited? It's like Christmas all over again for me, 5 years....I've waited for 5 years...it's been quite a ride, but I think it's in the next 5 years that it starts to get crazy amazing (spec statement).
UPCOMING DATA?
One of the slides that PAR showed us on 6 month data release back in April.5 of this year hinted at the kind of data that they were dealing with and analysing....
I've added my own Mozz Notes to their slide (see below), it's possible at least some of these will be again reported soon at a more granular level...linking the wonderful biomarkers we saw at Day 128 to potential structural sightings...
THE DATA CHANNEL
So where can this data end up? What are the possible channels?
Well of course the authorities in the natural first step....global...think FDA, EMA, ANVISA bit think local also TGA.
There are other parties like those circling Big Pharmas...there are going to be the ones that at least are already following us closely, but also consider the new ones to us. Oh yes, they will hear about these sorts of results.
Let me take a break for a sec though we're still dealing with channels... while researching for this Mozz post I came across a really interesting infographic...
Here is a graphic of the BP's...to give you an idea of relative size of BP in some of the main markets 6: (Single left click on the below if they are a bit small)
Ok coming back to other interested parties on our data...
The party that will also be most excited is the scientific community, I'm talking peer reviewers as an example.You get outstanding, first time seen, broaching a disease that to date has no viable solutions AND IS SAFE....you will attract some pretty decent peer reviewers wanting to cover the story. Our story.
Seminars, presentations, forums are all good channels for us to display our wares...... and guess what, we have one coming up real soon and it's a big and important one 7.
Prestigious? TICK
PAR PRESENCE? TICK
Abstracts? TWO TICKS (Two abstracts being presented by PAR)
Big? Well check out last year's turn out :
Some 15,000 attendees world wide?
... DOUBLE TICK
Paradigmers? Can any of you just imagine the convos the PAR team are going to have at this conference, dealing with Rheumatologists which is the precise area we are showing nutty good efficacy for the first time ever, yes DMOAD is all about Rheumatology?
Helllloooo? Is anyone out there reading this?
These convos may already have been good till before last week...NOW they can talk about 12 month separation between cohorts...where the line trends DOWN from Day 266 to Day 365... What am I talking about?
Ok here it is zoom'ed in a bit...that's a line trending away...trending down...down into the depths of sheer Mozz Nirvana...
..as if that's not enough....tell me what PAR are going to reveal in the next week (or two)...about 6 month granular...
I'll need two fans and an A/C.
Guys...keep your eyes on your screens and your fingers on the refresh button of your chosen broker......this next granular 008 observation set announcement could be truly.... quite a stunner.
he 008 program was always going to be a fascinating one. Yes the n was very very small...just 17 to 20 odd patients in each of the three cohorts...but the data? Oh the data....and it's ramifications...let's take a quick look tonight in regards to this program, at what we have and just what might be to come?
(20min delay)
