Pardigmers, this is going to be one of those Super Special long ones. Do grab a coffee (Italian or Irish it's up to you) and as usual, please do enjoy.
PROLOGUE
I'm not a massive gambler myself...I play cards with the boys maybe once a year on average...it's such fun times...with this crazy virus I don't think we'll be playing until maybe the end of the year if we are lucky...we have even flown to Adelaide sometimes just to play where one of the blokes resides. Adelaide is a nice city, Paul is from there... Love that Barossa Valley too.
I sorta dedicate this to Kenny Rogers who passed recently, I don't know many of his songs and I can't say I own a record (err young guys, a record is like a CD...ok younger guys a CD is the equivalent of a Spotify list from a given artist?!). He sang a beaut song called The Gambler which was about knowing when to hold them and when to fold them in terms of the card game called Poker.1 (Hey, not everyone knows about Poker, I'm not dumbing this down too much am I?)...PAR peoples, this song is for us...YOU have to know when to hold these you-beaut shares! Hold them till the world knows what we are and bids up the price...then show them what hand we have!!!
Mozza, what hand do we have? Keep a straight poker face and then show the world in a few years time.
In the old days, your knee would pain....as a typical guy (yes that's sexist these days, apologies but run with me on this one) we'd leave going to the doc it till it gets worse..ok finally we'd go in and see a doc.. the doc would suspect it's prob arthritis and send us off to radiology for an X-Ray. If we were lucky that X-Ray would pick something up.Fast forward to a few years ago...MRI...jeepers, what a break through...MRI'S are better for soft tissue and give you targeted 3D imaging. Yes X-Rays are better for bonier structures but in the case of OA, it seems MRI is the way to go. You can pick up a lot with MRI, gee technology has changed but you know what...the biology hasn't...., ol' Mozz goes one better than three Kings and two 5's...I got a Straight Flush (no that's not toilet humour). What do I mean...forget Ultrasound and X-Ray and even MRI...Mate, I got COMP research on my side.Who the hell is COMP, what does he bring to the Poker Table?
BACKGROUND
Paradigmers on the 29th of August last year we got the thrilling news2 that PAR has demonstrated that data from our Phase 2B trial showed that over time (53 days) the placebo group's COMP levels INCREASED by 2.1% (lowering is better). However, excitingly, the iPPS dosed group's level FELL and not by a small amount, a DMOAD potential of some 11.9%. This was significant.
Tonight I cover what COMP is and why does it matter.We know that "Osteoarthritis is a chronic and progressive condition"....we realise that it can "have a profound impact on every aspect of a person’s life".3 But we need an early warning system to alert us that we have a problem, we cannot rely on simply acute pain, it's too late when we feel pain, we need a test....somewhat like all the testing that some forward thinking countries like Iceland are doing in order to prevent the spread of Covid-19...They are testing everyone. No point in simply taking everyone's temperature, nah we need a blood test to see if we have the virus...that high temperature can come after a full 24 hours or more in some instances, patients can even be asymptomatic...This test that I mean for OA is simply the detection of COMP.
An AWACS jet, early warning devices. The military spends hundreds of millions on these such systems and we have one right amongst us too...we might call it CLDS - COMP Level Detection System?
WHAT IS COMP?
COMP stands or Cartilage Oligomeric Matrix Protein. Simply in Mozzie speak, this is the resultant residue when your cartilage is breaking down. It happens to us all to some degree as we get older...it is increased if we sustain injuries perhaps during sporting activities/injuries. Yes we need to keep active but it is the over-exertion, the injuries we need to try and avoid.COMP is a diagnostic indicator. Fundamentally it is where the balance of new cartilage production and the degradation of the same is off kilter and this destruction then presents itself as increased levels of COMP. Take a look at reference 12 in the reference section below for a more in depth look at what plays out, it gets quite heavy in regards to terminology and pathogenesis.
MRI - GOOD, BETTER....
Magnetic Resonance Imaging (MRI)... is good but there are limitations, eg. if you have metal in your body (including pace makers) or are pregnant then you aren't permitted to have an MRI...The advantages are that it is not an invasive method of seeing what's inside soft tissue like radiation therapies. It has another big advantage over X-rays, Ultrasound and even CAT scans - Computerised Axial Tomography (Mozz Speak, Tomography is just a sophisticated way of saying 'slice'), that advantage is quite simply the ability to look inside us in 3D utilising Magnetic fields and Radio waves. Amazing tech.
I first read about MRI back in 1987 - It's breakthrough technology. It looks like a scene out of Star Trek. Where is 'Dr. L Bones - McCoy' when you need him?
Sometimes a combination of diagnostic methods will be used to show the surgeon/doc different aspects of the injury or matter they are investigating. X-Ray images can also be quite useful specially to view bonier structures. Take a peek at Appendix A and B below for some comparisons of these technologies.
X-Ray -v- MRI, different details can be viewed using each technology.4
Enter the discussion of COMP levels into the mix...don't take it from me, let me quote from the master himself (Dr D Felson):
"In fact, in OA, where even magnetic resonance imaging may not sensitively reflect the consequences of effective therapy, systemic biomarkers may provide an excellent opportunity to identify whether a treatment is working in treated patients". 5
THE CLUE
Paradigmers....I have done a lot of research on PAR in the last year or so...I've come across some fascinating stuff not just directly in terms of what we own but indirectly from some of the other studies that have overlap with our molecule and give us pointers and clues as to what we own, and how it can be of real benefit to you, me and society. On the rare occasion I come across a snippet that's more valuable than the rest...rather than me feebly attempting to articulate, let me quote again from the master dealer of research himself, Dr Felson:
"...it is not clear that there are any current structure-modifying treatments for OA, the characterization of a biomarker whose change might parallel disease improvement or disease stabilization is extremely challenging." 5
For those that need some explanation. Let me extrapolate in my simple language... Dr D Felson suggests that at the time of writing, (May 2014) there is NOTHING that treats OA. He knows at this stage that COMP will change (reduce) if there is something that reduces OA articulated by the fact that he says it is "extremely challenging". Extremely challenging is what we have overcome so far...we get through Phase 3 and in my opinion we have the drug to tackle OA not just superficially but in Disease Modifying terms. Furthermore the Good Dr gives us this pearl also back in 2014 in terms of predicting the future:
"If biomarkers are selected that reflect the process of joint destruction and not static processes that have already occurred (like a radiograph), then a biomarker may predict what will happen to a joint or to the patient’s OA in general".
It's like back in 2014 the Good Dr knows in the future something will present itself and when it does it needs COMP levels to be reduced and then, and only then, we know it is the real thing...Paradigmers...in my view...that future is NOW. We have iPPS. It has reduced these COMP levels.I started this whole post with the comparison that X-Rays were good...MRI was better and COMP is the best at least in terms of OA detection...but that's just my interpretation...Dr Felson says it like this:
"In fact, in OA, where even magnetic resonance imaging may not sensitively reflect the consequences of effective therapy, systemic biomarkers may provide an excellent opportunity to identify whether a treatment is working in treated patients." 5
We are now on the other side...it's way past 2014...we have seen that our drug reduces COMP levels....it's a sure proof that what we have, works. Yes of course we need 1000 plus patients to agree (3rd Phase trial)...but this is just to satisfy the FDA requirements...we already know the future...how? Well COMP levels falling, by what was it? 11.9%, and the SAS patients actual testimonials that we have heard right here at PAR HC central..
OTHER EVIDENCE
There have been other studies too that explore this interesting relationship between this biomarker and inflammation, in the more recent 2018 study conducted by D. Hussein et. al.6 found that:
"Serum COMP was significantly higher in patients compared to control being higher in more active and significantly correlated with baseline synovial inflammation".
Yet another study documented also in 2018 which involved comparing and reviewing a total of nine other studies also found a strong relationship with their conclusion stating:
"The overall analysis showed significantly higher serum COMP in knee OA patients compared to controls which indicate the potential ability of serum COMP in differentiating knee OA patients from healthy subjects." 7
Par-Associates, a detailed study of the association of biomarkers with some 137 people was documented back in 2007 8 . In fact this research was referred by Paradigm themselves. The research suggested that:
"With the exception of COMP, none of the other biomarkers was a statistically significant predictor of cartilage loss."
Here is the key statement from that same study that can be found in the results section of the aforementioned report, I give you the Mozz Money Line ®:
"For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times (95% confidence interval)"
Mate, now that is what I call an association.
A NOTE FROM KENNY
"If you're gonna play the game, boy, You gotta learn to play it right". This means sit tight..learn all there is to know about YOUR company, Paradigmers, don't just listen to me, I am but a messenger, listen to the interviews...go through the SCIENTIFIC papers...research the past experiments and LISTEN...READ what the SAS patients like Happell...Like Ave Maria, HeyItsJay..there is also JTL..hear what they have to say..(Apologies if I have missed any others)......After all Paradigmers, every gambler knows...what's the secret to survivin'? It's knowing what to keep...I again turn to Kenny..."You never count your money When you're sittin' at the table....There'll be time enough for coutin', When the dealing's done".
Our time for 'countin' will come...it may be still a couple of years away...even 3 to 4 years...but it's a comin'.
ACKNOWLEDGEMENT
I have said in the past on the Hot Copper Forum when I have been asked how I burn the midnight oil....I often reflected back on you, the reader of my posts, it is because of your questions that I strive to provide answers, it's because of your constructive criticism and the great feedback that inspires me, I research under the guise of answering you BUT it helps me too..it adds to my conviction. Researching and writing about our company and getting your great feedback is not a chore for me...it is fun and I do enjoy it - I'm simply motivated by what a brilliant find we have in our midsts.
DISCLAIMERS
Most disclaimers are boring and no one wants to read them, in this one I'll give you some info. Things can go wrong...Even the most stable companies you would not think that could go down much, have gone down at times. I give you two examples:
1) STARBUX...such a stable and growing company... they fell top to bottom (75% fall)...not once but twice in their history of outstanding growth.
2) BERKSHIRE HATHAWAY...possibly also one of the greatest businesses ever, even this has fallen from top tick to bottom tick by 50% on four separate occasions.
Be careful...we do not know the future.
Yeah forward looking statements......DYOR...there is risk in most things...be aware of the risks not just of card games and gambling, investing too...don't listen just to me...we are on a winner with PAR like you wouldn't believe, "Now there's an ace you can keep".
APPENDIX A - COMPARISON TABLE BETWEEN IMAGING
(Reference 9)
APPENDIX B - RADIATION LEVEL COMPARISONS BETWEEN METHODS OF DETECTION
(20min delay)