What does that mean? At least by 30 % or so. There are already drugs out there that do address pain. How well they do it, how safely they do it, that's a different question.
2. A drug that improves functionality
No point in a drug successfully reducing pain, but the patient still can't move!
3. A drug that lasts, that is durable.
No point in having a drug that does the above two checklist points but only lasts a few hours...we need some patient convenience.
4.
Next on the checklist is a drug that is safe. In fact this point should probably be first on the checklist.There is no point in having any of the above if a drug does more harm than good. Corticosteroids is a perfect example of this.
Corticosteroids brings down pain very effectively, and the pain relief doesn't last a few days, most get 3 months, some longer...BUT...
...and it's a big BUT...
You can't use this too much, because there is enough evidence that they can destroy the very joint they are trying to assist!
Despite this, they are still wildly popular and wildly successful
1.
Paradigmers, what does that tell us, just imagine the scope of our market...speaking of which, thats next on the checklist.
Take a read, have a glance if you can't wade through it all, of the below...it's quite a read
2 !
5..
We need a decent sized market. Great to have all the above 4 points but what's the point of it's only a teeny tiny sliver of market potential? It wouldn't be commercial, it would be profitable, I wouldn't be posting.
6. Mate, all the above is super, but not so much if our product can simply be replicated/copied.
I'm not so much talking about FDA protection for x years, I'm not so much talking about patent protection for x years...i'm talking about just being able to simply copy the molecule and these generic cowboys selling it by the tonne. (Actually some of the generic guys are pretty professional, well they have to be in the larger Western markets for sure). They still have to rigorously comply with all standards and yes, that includes clinical trials.
Let me explain that a little more. Under a process called ANDA generics don't have to conduct full scale clinical trials BUT, and it's another BIG BUT....they must have the same active ingredient.
Tell me where are they going to source that active ingredient from?
iPPS has a billion combos. (Maybe lots of millions of combos then)....but it has a lot...and the process to come up with the exact same one isn't going to take place easily or soon.This is one of our most ultimate of protections, this is why a hostile takeover would be terribly hard and the chances terribly small. They would not only have to buy Paul and us out, they would have to have the blessing of the bene contract/relationship.
7.Whew...we made it this far...now we need to scale and we also need GMP...We have both. Our manufacturer (bene from Germany) have been producing this magic for not years, but for
decades. They can scale like you wouldn't believe. I'm not talking a few trucks worth...I'm talking whole trains (See what I did there)....
(Note: I'm talking a manufacturing train which is a processing unit or capacity).
8.We need evidence.
To really check and see how good our product is, how many patients it works for, and what any downsides are, we need early evidence. We have this already through Phase 2 but we also have it through a parallel SAS program, But buyer (holder?) beware that the SAS program is great to garner evidence but the gold standard is Phase 2 and more so, Phase 3. That's what we are about to embark on.
9.The next point on your Checklist is to have the 'nice to haves'. That's things like Peer Review, KOL support, and other preliminary signs.
A pal and myself did an interview with an FDA clinical trial expert who has had years submitting protocols for companies and observing what the authorities wanted etc. In one such interview he told us a few things to watch out for as our studies continued. One of them was to look out for recruitment rates. If they drop off or if it was getting harder to source patients then that is a red flag.
You want to avoid this if you are swimming at a beach, you want to avoid this if your recruitment rates start struggling during a clinical trial!
.This has been the opposite with us so far, it's not only been easy to recruit, there have been lines that have formed.
There is certainly a demand for a genuine OA solution to date, a solution NOT just for pain relief and function improvement, but a demand for the physical structural side too, the arresting of the progression of the disease.
Yes we are waiting for the Peer review but there have been peer reviews that have covered some of our mater to date, take wander over to the Appendix at the tail end of this Mozz Post for some examples..
10.Ok any good check list is going to have to cover what we have achieved in the past and where we are at now and what is to come...
Let's break this up in to the three paths.
A. THE PASTNow there is no easy and simple way I could cover this properly in just part of a Mozz Post. I'd need a few and you will just have to make do with a high level coverage. If you are a serious investor you'd skim through at least some of the threads on HC to get a sense of our journey so far.
In a nutshell...
Originally Paul and Ghosh worked on our molecule and at an early stage both realised what they had. Paul approached bene and struck up an agreement for exclusive supply. Oh so good this relationship became that bene agreed to not only extend the contract to an impressive 25 years BUT it is instigated from when we get our licence. It's quite the contract!
Now bene are the manufacture extraordinaire and again, I would need a few posts to cover them, I will include the bene factory tour as I know a number would not have read this one and it's a good story format overview of who bene are and that they mean to us. But from our side it's not like we have been sitting on our hands waiting around...
No, we have been proactive.
We have literally taken this company from a mere Pain and Function drug company to the next level.
After a pivotal 005 and now a 008 program we have the clear evidence that there indeed is a link between what is happening in the serum and the synovium. The synovium study was, well, in a word, revolutionary.
PAR showed us so many SURPRISES that we did not expect.
Look, so brainiacs amongst us might have suspected we could address in some small part the disease course, but let me tell you, no one, not even the statisticians expected the results we ultimately attained.
This is what we achieved in the most briefest ways I can explain:
- Heavy reduction in Wet biomarkers, including statistical significant falls of ARGS and COMP and CTXII. These are biomarkers that indicate observations of cartilage degradation.
- Chalk and cheese comparison against placebo. Not only we caused a fall in rates of cartilage destruction, we INCREASED cartilage. Not only we beat Placebo, but placebo went the other way. In other words if you went on the drug, your rate of destruction steadily and consistently continued on the progression of downfall....Active, our iPPS, reversed this course!
- We got the above sightings not over 3 years, we got it in 6 months. This has never been seen before this is what PAR are showing to prospective funders and prospective Regional Partners.
PAR over the years have engaged not just KOLS, but TOP KOLS. I'm not going through the list but there are a few scattered across the world. This, in my humble, will continue over the years. It has been because of Paul and his team's astute ability to attract the finest in the industry. Felson way back in 2019, to Kraus more recently a few years ago. We even have the famous Dr P Conaghan looking at our work in terms of the consortium he has gathered for the FDA. These points go generally unnoticed by most investors. They are influential and make an enormous difference to our journey. One small example I am compelled to repeat.
As a scientific researcher, if you are not half bad, you will have some few hundred citations to your name...Dr David Felson has some 150,000 citations, he is quite simply world renowned in this space. He worked on the FDA board for years vetting candidates in OA. For the very first time ever he came around to the other side of the table and worked with PAR to assist them in formulating the correct clinical trial program, this had never happened before.
I have met him only once and I only got time for one simple question.
"Dr Felson. I wanted to get your opinion on what you thought about Pentosan and the efficacy it is showing in the OA field..."
His answer?
"I think it's a promising therapy".This is only one check box in a whole swagger...but it adds to my conviction.
PAR spent months looking at the 008 data, they expanded the program mid stream and then they managed to incorporate the incredible findings which were off the charts into the P3. At the same time they needed to conduct a dosing study to find the Minimal Effective Dose. This added spades of time to the overall program. It's easy to grumble, it's also easy to forget what they achieved here.
Look, I also am a shareholder. I also thought we'd be done by now. But I'm also happy. Why am I happy, because I know once we are allowed to start, once we get the data back from a P3...this will no longer be just a simple pain and function Co. We will have structural observations on that label,
The above checklist can be further broken down in so many ways and individual parts, my aim was to cover it at a higher level and give some of the newer guys to us a sense of where we have come from...Let's tackle where we are and then where we are likely going to.
B. THE PRESENTSo where are we now? Well we are working in the background to get the P3 started. I think it is soon (I won't use the "I" word!)....I somehow personally believe that we need funding before we get to dosing...at any rate, PAR really do sound like they are ready to go! Clinics lined up, enrolments taking place....protocol in, no doubt the CRO's and clinics all ready to go too.
When will this happen...what can we do, just be patient and wait!
C THE FUTUREYeah this is what gets me going.
Once we genuinely start dosing, we do need to wait...but the great news here are two fold:
1] We don't have thousands to plough thru, 466 patients. It's tiny compared to other studies.
Did you now the Aspirin study was 22,000 patients strong
3 ?
2] We don't have years to wait for results.
Rightio, so I had a rough stab at this, happy for any of you to give me your thoughts on recruitment rates.
My logic is that it should take approx 10 months to achieve full recruitment. Recruitment is never straight line, it's usually a bell style curve, it takes time to get the first few patients in and then it snow balls. PAR will be very wary of getting this done on time and not dilly dallying too much. PAR have excellent experience in trial recruitment and progression, they have done it a number of times and they use the best. There are a few things to watch out for as we progress.
In the above chart I have my stab at the bell curve of recruitment, the important point for us in the halfway point, ie when 50% of the patient population are recruited, this I believe would occur sometime around November (see green shade above, that's when we get the 50% through, maybe I'm being slightly aggressive and it's more like Dec?), if you want to be a little conservative, call/make it December.
Disclaimer - remember the above is my own thinking, reality could vary significantly.
To this date we must add 112 days. Because the last patient to make the 50% number, like the others, will then need 112 days from the first of his/her first dose.
So, add 112 days to December and you get half way thru March 26', to this I would then comfortably add 6 weeks for compilation of data, dissemination of the data, recording into the DB and whatever else they need to do, which takes us to start of May 2026. I believe that's when we could have the interim read out. Again, to be a bit more conservative, you could easily call it end of May, or better (realistic) still, June 2026.
Paradigmers, I can't tell you how much of a proposition this is. If that interm just simply follows the course of the 5 well controlled studies to date, namely
- Kumagai
- Ghosh
- 005
- 008
- 002 ...
... we are done.
Now does the above all mean that we have literally 11 months of nothing?
No. I don't believe so.
I think there will be bits and pieces to come, and some will be impressive.
The single biggest news for us (after funding!) will be some sort of commercial agreement, I'm taking a regional deal.It might be, as PR mentioned at the EGM, a deal with a small hair cut....it might not be the biggest deal all time....but it will be a deal, a deal here is finally commercial validation.
it will lift the share price and it will not just cause a spike (my guess)...it will take it to the next base level. Yes of course there will be some trading around it. Some holders have nought in at 22 cents...some at 30c...they will be happy to say bye bye to us at 60 c...at $1. But a lot will be new buyers to us....a lot will understand what is to come in a relatively short period of time and they will hold on with gusto.
The other part of 'bits and pieces' could be brand new initiation of coverage, PAR road shows and getting the word out there that hey, we aren't far away.
Not far away from what?
Interim...first deal ...end of P3.
Once we get a first deal out of the way, like dominos, the next could fall...especially smaller regions that are more nimble on their toes will want to sew up deals with PAR.They don't need to wait for the big Readouts to occur, they will possibly get in early. The more deals we get, the more that SP is going to move.
The more it moves, well then the next large trigger happens for us...
The vesting of options.
They way I see it, you get one deal with a slight haircut...you cross over the 50% recruitment rate, hopefully it will get announced....you will generate excitement and the share price should be greater than 65 c. No brainer if we don't need ANY more money, specially if we won't EVER have another on market broad CR.
But Par-folks...it's what happens AFTER interim that will be the share price potential fire lighter...
When can we light a decent propellant under our share?What happens after Interim?
Well who knows, but if it is positive, if it's as consistent as we have witnessed so far...if it's as compelling as I think....BP will now get interested. Yes it will take some months, again we might find ourselves squarely in a boring patch and the SP dwindles or channels and we think, how long do we have to wait...but it is
this very time when things might just be going a little good-crazy behind the curtain at PAR HQ?
This is what I'm getting slowly excited about. We could find ourselves on this pathway soon.
Of course, it all starts with funding.
11. Now any good checklist is also going to have corporate and company fundamentals in there.
The tough questions like, do we have good management, do we have the finance...what is the outlook?
I can't pretend to be an expert in this particular field and I have to be guided by what the company says, the Corporations Act, the accounts we see and what goes on from a funding point of view. Yes this is the area with the handbrake on at the moment and honestly, unless this part gets solved, we ain't moving no matter what our drug does!
This is the next chapter for me. Again, as I have said, a few ask me if I'm worried about this segment. Again, honestly, I'm not.
Why? Because I believe the hardest part is over, and that's the Clinical and Reg side. It's the part where the FDA have sanctioned our MED, it's the bit where we have submitted our revised protocols and but I think it is easier to do than the Clinical and Reg matters I have touched on.
Now we wait. That's one of the harder parts...the waiting.
THE PSYCHOLOGY OF MONEYYou know, I had an alternative title for this post...I'll tell you what it was in a sec.
I'm currently reading a great book.
Back in 2019...we had a super suggestion for the poster
@Eire2011 namely Christopher Mayer's 100 Bagger book.
If any of you haven't read it, I also highly recommend it. I've read it twice, need one more reading at some point.
But the book I'm reading now (in-between manly Pentosan related peer reviews!!!) is
The Psychology of Money by Morgan Housel, it's a great read. But the chapter I just finished was on compounding and how impressively strong it can be.
But like drawing on some parallels with the 100 Baggers book. Share investment takes time. And time often means boring periods of months of nothing, no news, share price dwindling, negative
* comments on HC.
* = Don't get me wrong, we need to know and be across negatives, negatives keep us safe, negatives keep us alert, negatives is the fodder for growth, stamping out possible problems and researching to counteract them or escalate them.
So Morgan H. in chapter three chats about the story of Buffet and how he has been so successful but not just on an absolute basis but for so long and from so early in the piece. That is what is required. The parallel I drew with PAR is that many are waiting for more significant de risking opportunities and triggers. Some say they won't get in until we have a our very first deal. Others say, nah even that's not enough, we need our 2nd deal, then I will be confident. Still others proclaim they aren't touching this baby until there is the first dollar of revenue while a few conservative others might say that it needs to hit a market cap of $1 Billion and at least a year of revenue before they transfer money to their broker to buy shares.
That is all good and horses for courses and everyone has their own risk profile. But for me, I want in early. Usually I will be the little mouse quickly venturing out for a tiny crumb of cheese...but I have ventured out of my hole home many times and I like this mountain of cheese I have before me. Is it mouldy? is it edible, is there risk? Well perhaps. But what I have tasted so far I like.
Morgan states that there are some 2000 books written covering Buffet, there are of course many, many more about trading, economic cycles, strategies etc. Morgan puts it a bit more blunthly than Chris, he states, there are NO books are titled "SHUT UP AND WAIT".I kinda could have titled this post in the same way...
From the 100 Baggers book, Chris also suggests that most investors get bored. They can't wait a year let alone YEARS. People get frustrated at the lack of movement in a stream of water and promptly move to where the fish are biting, where there is movement...Here is a quote:
“Investors too bite on what’s moving and can’t sit on a stock that isn’t going anywhere”.― Christopher W. Mayer, 100 Baggers: Stocks That Return 100-To-1 and How to Find Them
STORY TIME
Ok how about this one....
This is taken from the Morgan H book.
(My interpretation of what Morgan H said).There was this guy, namely Heinz Berggruen back in the 1930's who fled Nazi Germany and went to the USA. Apparently he wasn't voted as most promising student when he was younger....he ended becoming quite the art dealer and managed a decent sized personal collection over a number of years. Some of his more famous works that he managed to acquire included Picasso as well as Klees and Matisses! He ended up in the 1990's selling his artwork collection to the German Govt for 100 Million Euro. But the German Govt viewed it almost as a donation as private art valuers valued the collection at closer to $1 Billion Euro! Heinz was happy to walk away with the princely 100 million figure. Morgan, the author's view, was that despite most of the art collection actually being worthless (an estimated 99%), it was the few select pieces that made the entire collection worth so much.
Isn't it the same for us?
We get this right, we get iPPS selling, we get a backer, the rest will be history. How many of us here reading this (and that still will own shares! And it better be more than just a dozen of us or I'm going to be mad at you)...will actually care if we 'only' have a few indications we are addressing? How many will mind once we are $15 plus...$20 plus...if things are going a bit slow and we haven't had a new indication out for a year? Yes I'm pie in the sky dreaming...but yes, this could actually happen.
A few milestones from now... we could be on a very different tangent working our way up the hill of good fortune.
My point?
Paul and Co don't need to get
everything right.
They may have passed up on deals in the past, they may have rejected too small an offer...they may have got timings wrong, they may have over promised in terms of some timelines...They took supreme risks, halting that 008 program mid stream, having to rejig it, pausing it and then reapplying for ethics was a massive risk.
Did they need to do it? Couldn't they have just plodded along with the original program? If they did...We wouldn't have had the independence of TWO clinical sites and importantly we WOULDN'T have had 12 month data, we may never have had a P3 with 12 months on there as part of the protocols. Remember, it's commercially driven...showing efficacy out to 12 months is next level for us. Yes it causes us more delay, more expense, more capital burn and more BOREDOM...but who here will be bored of a much higher potential share price, a much deeper market penetration and a much better insurance coverage to make it actually afforded to the masses!!
What market will we have once the average patient, the average doctor knows PPS can be used for pain management in general and can be used for multiple inflammatory conditions?PAR doesn't even need multiple indications, if they just get OA right we are totally done.
We have the following in the background:
- RRV
- ChiKV
- HFpEF
- ARDS
- MPS I
- MPS VI
...we don't need any of those in addition to OA to be wildly successful.
OA isn't just OA.
OA is linked heavily to Bursitis, ACL tears, Meniscus tears, DDD, it's linked heavily to psoriasis and RA. Gout is yet another indication that's linked directly.
Guys, we aren't interarticular...we are systemic, we address inflammation and that's just the major MOA. There are many more.
All Paul needs to do is get one deal right...all could potentially and euphorically change over night. It really won't make a difference once the share re- rates and new stronger insto power comes on board in droves. Any weak retail, any weak holders full stop, will be wiped out.
He doesn't even have to do a spectacular deal as the fist deal.
Imagine, what's our estimate for our entire Phase 3's cost? 100 Million?
If we get finding for half of that and PAR does a first deal of only $30 USD mil upfront with some milestones, that might be enough.
The options vesting even if only 82% of the holder base takes it up wudl bring is $0.65 x 90 million x 82% = $48 million odd.Add a little R & D rebate and we have made it, the rest will be totally academic, totally history. The SP will move from strength to strength, if interim read out hits the bullseye, maybe we could all of a sudden find ourselves firmly in an auction style bidding war with 5 huge BP's in the USA. It's totally game on.
An auction I want to see!Checklist yes, but at the end of the day, do you have the fortitude to wait? I've been waiting since 2015, probably really since 2018.It's long but it's not really that long, For a drug with this much potential, for a drug with this wide of a MOA list, for a drug for this much of safety and efficacy, mate, for a drug that can potentially address hundreds (not dozens, but hundreds) of indications. Crickey, I can wait,I am waiting...I continue to wait...I will wait.
Sometimes, we get ahead of ourselves...sometimes the best thing is to simply wait....sure, keep checking we are on track, keep debating and professionally discussing here at HC PAR Central...but if the thing is genuinely progressing...well that's when we need the patience to wait. Patience is a skill.
- Mozz
DYOR of course
APPENDIXPEER REVIEWS SO FAR:
https://paradigmbiopharma.com/wp-content/uploads/2022/05/20210805-PPS-Paper-Summaries-CS.pdfREFRENCES
REFERENCES1]
https://finance.yahoo.com/news/corticosteroids-global-market-report-2023-173100467.html2]
https://www.ncbi.nlm.nih.gov/books/NBK531462/ 
eah I was going to do another science post tonight (i got some ace material ready to go) but I thought that that isn't quite topical right now AND I ran it by a good pal and she said nah, less science, more checklist.
1.
(20min delay)