ometimes, we just need to go back to basics. Our share price stays suppressed but the science...oh the science, is the brightest I've come across. This is a story that is keeping on keeping on!
Tonight, a stellar paper...no no not mine, I'm talking about a peer review paper .....amazing evidence for a drug that you own...please now enjoy!
BACKGROUND
Back in 2010 a group of researchers led by Kenji Kumagai published a peer review in the prestigious BMC Clinical Pharmacology Journal.1 The researchers investigated Pentosan in the SubQ format and witnessed some pretty good findings!
Lets now explore.
Back then Hyaluronic Acid injections were more common, its only recently that it's been shown that there is more risk in these intra articular injections. Of particular note is that the researchers commented that due to the various number of different modality's, our iPPS at least in the vet industry is more than just a symptomatic relieving drug:
"From the results of previous in vitro and animal model studies, we have proposed that the spectrum of pharmacological activities exhibited by pentosan polysulfate sodium (pentosan) would qualify it as DMOADs".
The problem here, and certainly back in 2010, is that there were little human clinical evidence. Enter Paradigm Biopharmaceuticals and skip forward 13 years.
I'll cover a distinct link that does relate back from the Kumagai study to what we are going through right here and now. Look for this same link in the Fantastic Four section later in this post.
Part of this study was presented at the International Society of Orthopaedic Surgery and Traumatology (SICOT), in Hong Kong, China in 2008 and also at the Osteoarthritis Research Society International (OARSI) World Congress on Osteoarthritis, in Rome, Italy in 2008.
The trial itself commenced in November 2005 and concluded in Aug 2007.
HYDRARTHROSES
One of the main observations has to do with this term called hydrarthroses. This is the term for swelling of a joint caused by, you guessed it, excessive synovial fluid. It can also lead to Rheumatoid Arthritis.2
Now that you have this background....it was observed our magic juice had a positive effect on the cohort in terms of reducing this hydrarthroses. You and I both know what time it is now....
Mozz Quiz time!
Thanks for *so* many of you for filling my letter box with requests for Mozz Quiz's
Hey hey, enough already
Lets go.
WHAT PERCENTAGE OF PATIENTS IN THE KUMAGI STUDY ACHIEVED A QUICK REDUCTION OF HYDRATHOSES?
A) AH Mozz, you can't expect this to be too much, there are always a handful that it won't work on...let's try 7%
B) Are you kidding me? it has to be more - let me guess 15%
C) 25%? Quarter of the full cohort?
If you picked B or C, you were pretty close...
Answer ??
...it was 100%
Yes, all of them....
"The hydrarthroses were reduced quickly in all cases".
MORE?
Oh yes of course there were more Pentosan induced positive observations...
"The ROM of the knee joint improved significantly "
Chart please Mozz?
Of course:
Ok I get a drug working in the first few weeks, when it is fresh and all...but look at the stars of significance above ...all the way out to week 52??? Mate...I cannot tell you what commercially this could mean (spec statement). These significant improvements were being maintained at the one year follow up???
A WORD ON MOA
Kumagai et al. elude to Ghosh's work and they list some of the poignant Mechanisms of action:
Pentosan increased the amount of proteoglycan incorporated into the extracellular matrix.
In the synovium, Pentosan increases both the synthesis and the molecular weight of hyaluronan.
Pentosan has anti-inflammatory function and strong fibrinolytic activity, which improves the blood flow not only in the synovium but also in the subchondral bone.
There are many posts I can do on the above and the many other actions of Pentosan...I can see myself doing this for some number of years! There is so much material and just wait till the world gets a real sense of our drug....there are going to be a number wanting to know more.
EVEN MORE EVIDENCE
Pictures? You want pictures...take a look at these beauties:
Its like for 7 straight weeks Pentosan is hammering down the pain, abating it, banishing it back in the box....reducing the NGF source production and allowing cellular repair and stimulating new growth of the cells. For it's cumulation effect is so wonderful and pronounced that by just week 7 the body finally kicks in and makes use of the restored balance between too much inflammation and not enough time to actually solve the underlying causation. We see this in the wonderful display of significance in terms of pain reduction from week 7 onwards...but it lasts. Boy does it last...
Energiser bunny anyone?
Great Ad....I do hope one day our Global OA Partner either comes up with the slickest ad OR has the MOST consistent labelling and marketing?
It's at least to Week 52 that the pain is lower..
Mate. If there is a drug that addresses pain in a meaningful way...and if you are telling me it is safe AND I don't have to keep injecting myself week on week to perpetuity AND this magic LASTS for at least 52 weeks and by the end of it I either may not need any more injections or perhaps a couple of boosters for the next entire year....I want me some of that.
Then you additionally tell me its not intra articular? Its not that I have to have it in each and every aching joint? One series of SubQ injections far removed from the actual joint site is enough?
INTRODUCING THE FANTASTIC FOUR
Indeed what is the link between a researcher, Kumaji and the Fantastic four....well I don't actually mean these guys above, the super heroes...
I mean the FANTASTIC FOUR BELOW....
ARGS
COMP
C2C
and CTXII
A closer look at the Fantastic Four?
Those that have been following me for more than 2 years will know that I have reported on ALL of the four E X C E P T C2C....
The Fantastic Four...fantastic because we want meaningful reductions and these are the guys that have been identified as giving us clues that Pentosan is working from a histochemical point of view. They are of a prognostic nature...bring them down and you bring down Inflammation. Bring down inflammation and you bring down OA. Bring down OA and it's a world first....have a world first in terms of this last remaining disease and people are going to pay up.
...and in particular one of the Fantastic Four, one where I haven't seen a lot of specific data on. Yes I've seen some wonderful results of iPPS specifically on CTX II....but not so much in terms of C2C.
Before we uncover the data set...a little background on what this C2C is and what it can tell us.
Fundamentally, C2C is simply a cartilage degradation marker...you see more of this in the urine, you know your cartilage is disintegrating....
"The significant relationship between C2C and JSW in IHOA suggests that this marker is of value in assessing cartilage degradation patients with involvement of a single joint". 3
C2C Has been identified by the research conducted by Dr V Kraus for the Biomarker Consortium...how about this quote:
"In conclusion, uC2C may be a promising candidate as a prognostic biomarker for kOA progression". 4
SO now we have a sense of why our KOLs have chosen C2C as one of the super 4 biomarkers to chat to the Authorities about.
RESULT SET
Remember, I have NEVER come across Pentosan's specific action on C2C, I read this for the first time a couple of nights ago. I suppose I may have come across it in the past, but I'm focussed on it now that it has been identified as one of the Fantastic Four AND indeed it provides evidence of cartilage degradation.
Lets have a look at the data from Kumaki :
The researchers comment that its one thing to have ROM and VAS measures but from an objectivity stand point, C2C is in a different class... "as C2C is said to be the only reliable marker of cartilage metabolism".
Indeed there is another research team that also investigated the relationship between levels of C2C and Hip OA.
Their conclusion also was telling:
"The significant relationship between C2C and JSW in IHOA suggests that this marker is of value in assessing cartilage degradation patients with involvement of a single joint".3
I rest my case your honour.
Fantastic Four indeed....when PAR go to the Authorities with such great data, as I have said in the past, I would LOVE to see their reaction when they read through the data and understand what exactly there are dealing with and when they get a real sense of where we may be going with this one.
I often state randomly...do you know what you own., do you know what this could be valued at one day...do any of us really know the numbers that will at least try Zilosul?
- Mozz
DYOR as per usual
POST SCRIPT
While researching for this topic I stumbled across another research paper from a Japanese team, I recognised two of the researchers...I have come across their work before, see red underlines below:
In the paper above (reference 5), it has some direct relevance to the Fantastic Four.....its via COMP. Now PAR in the past have mentioned COMP a lot and indeed we have seen some really cool data and signs on ol' iPP's effect on bringing it down...Here is a small taste if you are new and haven't managed to walk down the catacombs of our previous stellar releases:
Here is a quote from the team (Hunter et al.) that came up with the statement above that a single measurement of COMP predicted cartilage loss....what do you think the fold increase is for every one unit increase of COMP?
"For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times".6
But guys, one more first for me...how about this chart below to show how COMP trended down in our equine friends....a very telling chart and one that I couldn't resist showing you....do I feel like the kid at prep grade at show and tell when he has such stellar news that he is busting to keep his hand up raised as high a possible so teach (FDA!) will hopefully see him?!
Three separate dosing cohorts in the study above on horses....placebo (0.0)....intermediate strength of iPPS (1.2 mg/kg)...and finally the stellar results (3.0 mg/kg)....The lines are literally bending from upwards...to plateau and then wonderful trajection LOWER with the closer to optimal dosing of iPPS....
ometimes, we just need to go back to basics. Our share price stays suppressed but the science...oh the science, is the brightest I've come across. This is a story that is keeping on keeping on!
(20min delay)
