PAR 4.55% 23.0¢ paradigm biopharmaceuticals limited..

iPPS and Long Covid, but first a Prologue & story...

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    PROLOGUE

    One of the reasons why our share price is smashed is because finally there are more sellers than buyers, simple. Sure, there could be so many individual and grouped reasons for that. At the end of the day at least we need to ask, WHY are some shareholders selling out? I mean why would you sell when there is just so much potential?

    Potential to address Pain
    Potential to address Function
    Potential to tackle MULTIPLE joint pain ALL at once
    Potential to address not just one type of Arthritis but several if not all forms....from OA to RA to Alpha Viral Arthritis.

    Why would one sell a stock that controls a drug that has so far proven to be safe?
    Why would anyone ever sell a share that pertains to a company that has a drug that one day may address MORE than just OA...I'm talking pain in general, a massive huge market....multi multi billions.
    Why would you sell a share of a company that not only has future access to such gigantic markets but there is literally NO competition in this space. Nothing that is as effective and certainly nothing that is as safe or as durable?
    Why would you sell a company that has a non addictive and yet effective drug that patients are raving about and have declared their stories?

    There is a chance that the average patient that derives efficacy (and around 90% so far, do) may have an enduring pain relief. During this time they will be able to avoid nasty medications with known side effects.

    There is a chance that in at least SOME cases there will be a DMOAD effect, yes that's at least SOME regression of the disease and in some cases there could be an actual chance of cartilage regrowth!

    There are good chances that a lot will AVOID surgery.


    Why would you sell?

    Because they may not know all of the above.


    ISLAND TALK

    I like to think we at PAR Hot Copper Island know just a fraction more than the average shareholder in general. Mate, who has evidence like we have? Who reads through scientific publications, of those holders that are selling down...do they know what's coming, do they know the potential and can they wait? These are the questions I ask. I don't think they do, no and no again would be my answers to that.


    https://hotcopper.com.au/data/attachments/4134/4134935-ee2a90610dd87930cd2470ce90eba719.jpg
    All alone...for the moment...


    We are very very lonely on an island..we wait and wait for a bridge to be built to connect us to the world...not many at all know about us, probably not many believe us...and not many as yet are willing to pay for us....but this, in my opinion will not always be like this. Word and evidence will eventually seep out. I am not sad...I am not worried....why? But our share price is crushed, all is lost...sack management and stop the trials? Are you kidding me? Nothing has changed.

    What do you mean the share price is low...long termers don't care too much....has the drug stopped mid path? Has one patient come up to me and said :

    "Mozz, I love you buddy, but iPPS doesn't work and in fact I now have higher blood pressure and I'm losing my hair as much as my mind".

    Have I stopped seeing any more research into our drug and am I starting to read peer reviewers saying this stuff is junk? The light of iPPS is MORE brighter than it was 2 years ago...This article (see below, its coming after my soap box talk) only adds still more weight.



    THIS ISNT THE LAST DIP

    I was just chatting to a good mate last night and I said to him, you do know this wont be our only share price dip. We will have others along the way...sure we might be at higher prices compared to now, we may one day find ourselves at say $5...maybe $10...and then we will fall again, we will wonder why, there may or may not be reasons we can glean for this...but we will dip...its part of how shares go...

    I can even see us dipping hard when we finally get registration....even first sales. We will all possibly look at each other and wonder how is this possible, there may still be a lag in share price for some time after first sales...(again we should be at a higher base than now of course)...but we will wonder about this and what's wrong and WHY....it will take time for people to understand what we have is REAL. There could be a lag, I estimate months before our share price picks up from a dip after registration and then people start reading the sales in the Quarterlies and finally it will take off. Of course there could be deals that will propel us to higher levels before first sales...but dips are always possible...people with shorter time frames, people that trade, speculators and manipulators are always going to be around. When I say this is a long term play, I mean it...I also mean that it can only be the resolute that can hold for that long...through thick and thin.



    THE COST OF SELLING

    Now look, I'm not impractical, there are many that cant wait for so long, that don't want to wait for so long, that are happy with some profit....I get it. I also get that some smarties can take their money out of this, play something else and come back, or maybe never come back. I couldn't do it. I've tried to be smart in the past with other good looking stock stories and finally those ran away from me after I sold out and I was left holding what, 90 shares as the company went global *ugh*. Not doing it for this one, there is just way too much potential. (My views).

    So, I had a busy night last night, I talked to another mate, Lets call him M. I've mentioned him in the past, I haven't chatted to him for literally a year now....we had a great catch up...he told me a story...

    He had a mate and back when CSL listed he had the good fortune to buy just 1000 shares...at $2.50 a pop. Nice one...M said that his friend sold out a long time ago when it made a 6 X. But this friend of his regrets it....the effective price is now $1000 (dividends and splits included)...

    Yeah Mozz, its only 1000 shares....


    1 0 0 0 multiplied by $1 0 0 0 = $1 Million


    The trick is to have a holding, crystallise some on the way up makes sense, but I at least am holding a core, I will not sell these even if we have dips more pronounced than some of those roller coaster rides at Disney World. Why sell if the story is still good, I don't give a sh*rt about the current disconnected share price...find something else to distract you, take $5 and buy some other share that goes up more than us as you wait patiently.

    Don't forget, I'm not burying my head in the sand..if there is a genuine concern, we want to hear it...always...just do it constructively and professionally.



    BUT DONT TAKE IT JUST FROM ME

    If you need some real inspiration get it from Warren Buffet...his simple advice:



    "I've been taught by Ben Graham to buy things on a quantitively basis, look around for things that are cheap."


    "...understand what the economics of the business are likely to look like 10 years from now or 20 years from now".



    "Buy stocks below what they're worth".




    Its only after some time our share price will finally start moving....and its THEN you will rush to your broker accounts to see how many of these golden Willy Wonka tickets you own. I know there are delays and timetables being pushed out...I know that sometimes we wish there was more we could hear and sooner....I know that its immeasurably frustrating that we have possibly one of the greatest products in the world, and yet we do not have sales still. Mate, Do I know how hard it is to endure an upside down share chart...how can we be falling so much when things are just going so well for us....where is the rationality here?

    But let me tell you this, we aren't the first company with an outstanding product to find a disconnect with our share price. I also know many can't just sit here for years and years and wait. We also have to be practical. What I can do is to bring you evidence as to why this product is any good and what COULD one day be our potential. Not saying there is no risk...you still need to keep your ears and eyes open...keep pestering who you have to pester to make us a better company...its for our good.

    The rest is up to you. What do you do with this investment...I know what I'm doing...sitting tight.





    Let's check out some more evidence then....


    https://hotcopper.com.au/data/attachments/4134/4134965-31b83f4c23f22040fddb2de309a22ec7.jpg



    https://hotcopper.com.au/data/attachments/4123/4123747-c5131aba16b32a99b497df56310e25ff.jpghere are a number of articles being published in recent months and its quite easy for us to miss them. Now I can't profess to be the radar in this case, that title goes to this mysterious man from the West again....I queried him the other day:


    https://hotcopper.com.au/data/attachments/4123/4123753-4c82db8245bae0d6470a1a658d244081.jpg

    Are you affiliated with Reuters?
    Do you belong to the famous Associated Press syndicate?
    What Journalism Degrees have you acquired and what search engines do you employ?


    I again acknowledge him for finding some of these great papers. I, like many of you, am but a humble benefactor.

    Knowledge is wealth. If we find ourselves in a market that doesn't CURRENTLY value the diamond we posses, simple, don't sell!

    One day they will revalue us..


    As per usual, these are only my interpretations, the science gets heavy...I could interpret the wording's incorrectly, I'm no scientist. Always better for you yourself to do the research and come to a given conclusion as to whether this is compelling for you!

    Please now enjoy,



    INTRO

    No awards can go out to anyone that has heard of Covid and though things look a fraction rosier for now, Long Covid exists and mutant strains are still possible. Some 5.17 million lives were lost over the last two years. Its a different world. Despite me hearing some 10% of the population that have acquired Covid to date that have Long Covid, thankfully we have some solutions and for those that are sicker than the average, at least there are some medications that can provide relief.

    However, one of the newer remedies in the future might just involve you and me....

    Tonight we cover material from not ONE very recent Peer reviewed doc, but from TWO and you know what, excitingly BOTH have PPS as their central drug for discussion.


    https://hotcopper.com.au/data/attachments/4135/4135009-8e1aa2893c520b2d81dd37c0bc9bf81f.jpghttps://hotcopper.com.au/data/attachments/4135/4135013-578c7d0c63fea1797c6360fa709639c0.jpg

    Not one, but two peer reviews on this subject? Magnificent.




    Lets start of with a quote....hey, who am I kidding, this is a Mozz® post, lets start off with THREE quotes:


    Covid cell infection is "...strongly dependent on theinteraction of the virus-surface Spike protein with the glycosaminoglycans of target cells".1


    Key word from the above is glycosaminoglycans. Pentosan in itself is a glycosaminoglycans-like molecule. The researchers Herrero et. al. described our molecule stating, "...we describe the promising therapeutic potential of the glycosaminoglycan (GAG)-like molecule pentosan polysulfate (PPS) to alleviate virus-induced arthritis". 2

    The second quote gives us a sense of this GAG element again but adds the concept of the relationship of Spike, Ace and Gag:


    "Pentosan polysulfate (PPS) is a natural GAG/heparin molecular mimetic derived frombeech trees, which is in clinical use, but not as a blood anti-coagulant. Since we intend toprofile the Spike/ACE2/GAG axis as a novel therapeutic interface for the treatment andprevention of SARS-CoV-2 virus transmission, a compound with less potential side effects(e.g., bleeding) than heparin was investigated".



    I'll cover just what the Ace receptor is a little further along in this post but I thought this was a pearler:


    "Only PPS was found to interact with ACE2, with a high binding affinity of 585 nM.".1



    Covid itself can be quite varying in clinical manifestations as we know, from zero symptoms, asymptomatic through to mild cold, fever, slight headache, to a completely overrun of cytokine storm and respiratory failure and unfortunately death. It is via the respiratory system, read "lung host cells" 1 and the interaction of the ACE2 receptor gateway into the cell that causes a boatload of damage.

    The researchers investigated the use of a drug called Enoxaparin, this one is used to alleviate blood clots ion the lungs, however it comes with warnings. Their investigation of PPS and Enoxaparin based on the results were summarised by the statement,

    "We can therefore assume, that both, Enoxaparin and PPS, are potent anti-COVID-19 compounds which prevent viral spread in vitro, and are highly efficacious at low active doses.".



    ACE2

    Ok this Covid stuff gets complicated, I'm going to do my best to try and explain it, if I get anything wrong, do pipe up...this is only my understanding of the detailed science


    From what I can gather Heparin interacts with the SARS-CoV-2 S-protein with high avidity (Mozz word for this; enthusiastically!). Now Heparin Sulphate on a host cell plays an important role as a co receptor . The other receptor that this nasty virus uses its spike is a receptor (as seen above) known as ACE2.

    Now I know there are a few of you that are going to be lost in a sea of scientific words...hey, I'm sorta there with you...so lets check this out as a diagram: 5


    https://hotcopper.com.au/data/attachments/4123/4123833-66d3efc3b9cdcfa5f9b08e6e47797ec0.jpg
    Not one receptor, but two, namely ACE2 and Heparin Sulphate.



    So these smarty pant researchers took a few compounds and observed HOW these components worked on this relationship.


    First lets take a look at what compounds they trialled:


    1. PPS
    2. MPS (This is a hydration agent known as Mucopolysaccharide Polysulphate, typically used as a topical treatment).
    3. Sulfated lactobionic acid
    4. Sulodexide,
    5–8: Defibrotides,
    9–14: 4-t-butylcalix arene-p-sulfonic acids.


    Rightio...So what we are looking for is a reduction of the affinity. In fact we want the % of inhibition to be as low as possible. We don't want to allow the nasty Covid Virus to be at all docking to our cells.



    https://hotcopper.com.au/data/attachments/4131/4131050-311ba67b608d07b863bd49131cad72a9.jpg
    This is a docking we want to prevent....Do not allow the Covid Spike to dock to the cell receptors!



    So lets take a look at the result of these compounds:

    https://hotcopper.com.au/data/attachments/4131/4131052-63e075300fa58b0bd6d879b876111840.jpg


    So all the above various compounds were tested in terms of their ability to effectively block or disallow the binding of the unwanted virus to the cell's receptors.

    Umm Mozz? Love your attention to detail but #1 and # 2 bars are missing?!

    Yes..err ..yes of course...Well I did that deliberately so YOU could GUESS what the percentages were for #! (PPS) and #2 (MPS) (Note: Don't get the 'MPS' above confused with the MPS indication we are pursuing separately to OA, totally different concepts).


    Ok what are your guesses?


    Hmm maybe 34% ..possibly lower?


    Wouldn't it be great if we get 20%?


    Ok here is the chart, the unveiling of results *Trumpet fanfare* :




    https://hotcopper.com.au/data/attachments/4131/4131063-8cb3a593fab1389300b6b23cd3b61cd5.jpg



    Umm Mozz?

    Sorry mate, you have made a mistake again....you still haven't revealed the readings....you just have a couple of dormant stars there in the missing columns??



    Umm guys?


    I didn't make a mistake.

    Those two asterisks ARE the readings....




    It was zero....


    PPS (and MPS) TOTALLY INHIBITED the virus.



    If you need to see this for yourself, check out Reference 3 - It's a tough read...but you'll get the picture.

    Mate....total inhibition. These words are music to my eyes.





    CONCLUSION

    I could attempt to put a conclusion together myself, but lets hear it from the researchers, (My bold emphasis added below):

    " PPS and MPS in solution showed remarkable inhibition activity against chip-surface heparin binding with the wild-type S-protein RBD ".and further "Finally, we confirmed the neutralizing effect of PPS and MPS on SARS-CoV-2 pseudotyped virus in vitro ".

    When I first mooted that there was efficacy against viruses some two years ago (27th of Jan 2020), I was laughed at by some...



    https://hotcopper.com.au/data/attachments/4134/4134227-08e20ecc1413c4312d3417ffb1baefe1.jpg
    The above post caused a bit of a stir for some, too hard to believe we could show efficacy against a VIRUS! That was two years ago...skip forward to today....we are just getting peer reviewed qualitative evidence back...can you imagine our position in another two years from now? What about 5 years from now? I might have staff in 5 years! (Maybe 10?).



    No probs...but I don't think they have the last laugh....as summarised again by the researchers: "These results suggest the potential use of PPS and MPS as therapeutic and/or preventative antiviral drugs".

    The word used by the researchers just above sums it up better than I can....



    One word,

    "Remarkable".











    POST SCRIPT


    https://hotcopper.com.au/data/attachments/4135/4135034-21d8b20a04cec6dc5d14a62dfe468b1c.jpg

    A bit like those Marvel Movies ...for the smaller fraction of the audience that sits through the credits (and endless stunt people and graphic artists)....here is a tiny fact you may not have realised...Covid 19 is a member of the (SARS-CoV-2). Its a term I'm sure you guys have heard...but did you know what SARS actually stands for?

    Severe Acute Respiratory (Disease) Syndrome

    Guys...ARDS is a well known indication that PPS acts on. We are talking about something that is already being researched by us! Its also on my list of to do posts though I have covered it in the past before at a high level...more new info to come!

    I just need more time.





    REFERENCES


    1] https://pubmed.ncbi.nlm.nih.gov/35052728/
    2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505659/3] https://www.mdpi.com/1424-8247/15/2/258/htm
    4] https://www.lung.org/lung-health-diseases/lung-disease-lookup/ards#:~:text=Acute%20respiratory%20distress%20syndrome%20(ARDS)%20is%20a%20life%2Dthreatening,hospital%20for%20trauma%20or%20illness.
    5] https://www.sciencedirect.com/science/article/pii/S0092867420312307
    6] https://www.drugs.com/mtm/enoxaparin.html
    7] https://www.practo.com/medicine-info/mucopolysaccharide-polysulphate-2681-api#:~:text=Mucopolysaccharide%20Polysulphate%20is%20a%20topical,injury%20has%20healed)%2C%20etc.
    Last edited by Mozzarc: 02/03/22
 
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