hat pre-tell does concrete have anything to do with PAR, Mozz?
A number of new investors are asking...must we wait? Why cant PAR just do a simple P3 trial? We know, or suspect we know, the drug works....we have a number of patients (Phase 2, SAS, EAP Ex US Footballers) where we can see at least a good chuck that are getting efficacy, we hear it from super star HC posters...lets just do the min. and be done with it?
Not that simple...we need a strong concrete base.
ADAPT008 was originally planned as a simple 2 pronged study...placebo -v- active, done, simple, no worries...lets check out the synovium and the biomarkers and see what we see.
Nah, our base changed...we added 12 months...we had another site AND we added the once a week dosing. The ratios changed to 1 : 1 : 1
We have adapted, this isn't a short term thinking company. No short term company would make the hurdles harder. The same was true for the pain threshold being set at 50%. To be commercial one must show around 20 to 25% pain reduction.
WE AREN'T A THIN LAYER OF READY-MIX INSTA KINDA COMPANYMate....people ask me, Yeah Mozz I get the 002 main trial, I know that the FDA often and frequently suggest a confirmatory trial, that's our 003.
But seriously Mozz...what's all this with 006, the 007...009 and now we even have a 010. We have more numbers than on my screen on Tattslotto night!
More trial numbers than we can handle?New guys to Par....these studies provide us with vital clues....specially if you have a longer term mind set.
Paul gave us the clues in a long interview with Scott Williams some time ago.
The logic is as follows
At the end of the day, the Golden Mozz Concrete award goes to the company that has the toughest, strongest and broadest base. Why?
Cos it gives us options...we are no longer restricted to a one storied house..we can go up a number of levels in the future. What does this translate to?
Well firstly if we were to do just a simple 002 and 003 study...on Read Out yes we would all be partying initially (spec comment subject to clinical data)...but then we would need the box of tissues, pronto. Why? Because the FDA would start asking the next logical questions...err Par? How LONG does this treatment last for? What is your re-treatment profile like? What is the typical duration at? Yes Par, we know it was safe in the first course, but what about retreatment? Are there any toxicity issues or concerns we need to be aware of? Is there a build up of the drug over a year or over a course of retreatment. Yes we agree you have a good looking candidate, but lets work on these extra requirements first hey?
There can be nothing more frustrating for me if we have a great read out...we launch our r*cket only to have a flame out...and then another complete study and thus delay before we get that all important licensing.
Take the pain now...take it up front...rip the band aid off and then we have blue skies to contend with...
Go on, just do it ...for the betterment in the longer term.Here are the numbers at high level:
006 - Extension study for main trial (002)
007 - Extension study for confirmatory study (003)
009 - Retreatment study
010 - Hip OA study
It is the above that attempts to get a lot of the pre-emptive questions out of the way, that we will be asked after read out of our main trials. It is also these that will add credence and value to the label and also show the KOL's how comprehensive our data is before going to market. You also know who is going to be curious about these before being made to pay up? The insurers.
However, if we didn't do the above studies....we wouldn't know the answer to many of the ensuing questions from the authorities...we would then have two paths ways at that juncture in time:
1) A very narrow label saying we are constrained by the fact that yeah this stuff worked in a trial...but we got no clues about anything else really.
2) We have to quickly set up studies to investigate. (And you and I know there is no such thing as QUICKLY in a clinical trial design, set up and then execute further studies)
Do the hard yakka upfront, so once we have a green light...well, its full speed ahead.
This frustrates the shorter term mind set...the shorter termers want their 100% profit and they are out...they are gone.
Yes of course we all want this to rise and rise quickly....but when we have a much bigger and lucrative longer term story, I think it will definitely be worth the wait.
ACE THE ASSIGNMENTWhen a teacher at school asks you to research something, who gets the A+ ?
Is it the kid that just answers the question and is done? Or is it the kid that answers not only the question but within reason, answers the surrounding questions, they give a short historical background, they talk about other issues related to the assignment topic, they cover the future and really deal with the subject of what's being asked. This is the A+ student.
Is it not in the same way that PAR has added extra hurdles because they want to excel? Because they don't want to just double in value in the next year or so...no no no no they are looking for a world beater...they have learnt the CSL lesson...they are doing it APPLE style. Apple is not a tech that is cutting edge, its slightly behind...but it is quality, it is an encompassing eco system...it is simple for the novice but aptly complex for those that need the detail. Its aspirational.
Apple does not just stop and end with the iphone..they build an entire eco system around their most popular device. They link in Apple Music...they go after thousands of apps and make it easier for others to build aps that will work on their system.
Are we not of the same stature. Do we not have the one core product but are building a huge arsenal of advantages and future indications?.
We have safety
We have pain reduction in joints
We have function improvement
We have the practicality of being able to be stored at room temp
We are working on patient convenience in terms of application
We are durable
We aren't intra articular
You don't have to inject each separate aching joint, its multi acting, simultaneously
We can cater for repeat customers
We can scale
We are linking this to first time potential halting and in some cases REVERSAL of the last of the remaining large disease.
But your company doesn't stop there....
Once week dosing -v- twice is being looked at as I type...
Rescue medication times between Placebo and Active are also being investigated (*).
* = I will include a separate post on rescue medication, what it is, what are the ramifications in a post below this one for those that haven't seen it.
..
Mate....all of the above points is music to my apple ears..
Another Global phenomena?...but I'll go you just one better, actually make it two:
1) We could address all types of pain
2) We could address many more inflammatory conditions
1 and 2 above is something I'm keeping my core for. Yes yes of course I will be excited over a X2 and X5...but what X are we looking at if 1 and 2 can be satisfied in lets call it 8 years...Its a party I still wanna be at.There is just no way I'm going to be left with circa 100 shares at this point, I'm learning from my mistakes...
GO DEEPERFor a solid concrete foundation we must simply go deeper....
If I have a small exposure to a share, lets call it 0.5% of my holding in one company, sure I take a look every now and again. I actually have totally forgotten about a few of the real small holdings, a couple have nicely grown without me touching it over the years!
But if I have a larger percentage holding in a stock...(any guesses which stock that is)...I'm going to wanna be doing some research. I want to understand what we have...why it works,,,,who is on the radar in terms of competition. What are the alternatives from a patient point of view ....what are their choices of treatment (lack there of)...how will the disease typically progress...why are we going to be successful?
I don't want to JUST read it from a book...I want to build my OWN empirical evidence...yeah man, I want to actually hear it from others that have tried it...I want the stories...I want to hear what they faced BEFORE..and what it did to them AFTER.
But I'm not unrealistic and blind. I want to know the stories from those that it DID NOT work for also....I want to know what they experienced, was it bad...did it have any lasting repercussions? What are the negatives...give me the ghosts so I have an all round complete picture....warts and all.. I want to know how this super vehicle will perform when its raining. When its icy...when the conditions aren't good.
Performance in all round conditionsI want to go so deep into this company that its bordering on nutty, I want to know more about the molecule, I want to know more about the protein pathways...the cytokines...the chemokines..I want to know all about what is under this hood.
I want to walk away from a showroom knowing I have exactly what I want. Sure I will listen to the salesperson's spiel but let me tell you, I'm going to go to the average Joe in the street and get his or her opinions, how does the car handle...what are the problems, how can it be improved?
That's the research I'd do for a depreciating car....imagine what I want from a potentially APPRECIATING STOCK!
Definitely, Go Deeper.
Ok lets get back on topic....so yes, I want deeper...another name for this is Market Penetration.
Its another entire reason why PAR have taken their time very carefully setting up the perfect trial design...getting experts, (Yes Dr D Felson, I'm looking at you)...as well as consultants and research and recommendations that are out there...why? To get a deeper market penetration...how do you do this? Ahh that requires a whole new sub topic:
ITS ALL ABOUT THE DOCTORSUltimately who will prescribe us?
Who will take their beloved patients that they have been treating for decades in some cases, where they have very close Patient relationships? Well the Docs....they are the ultimate front line for us....yes our Big partner will have a say in what they can recommend to the Docs but finally when a BRAND new (repurposed) drug comes along in an area that has NEVER had a DMOAD (subject to trial) they are going to have some questions, let me tell you.
The first thing the Docs are gonna do is go to the label, they will check it with the association. In fact the associations themselves are going to want to see this....it will be this label that will ensure how deep we actually manage to go.
Yes yes I do calc for myself based on just 5 and 10% penetration rates...but our go to example, Humira, achieved some crazy 65% market penetration.
The trick with Humira is that they didn't have any competition, they incrementally added a few new indications as the years went by....and what do you think happened to the prices they charged over time? They increased...take a look at this chart:
They could do this because there wasn't much, any, competition. What about us?
Before we continue, here is an updated chart of Humira's sales
2 for you to digest...can you just imagine this, for a product that is black labelled, has a number of warnings and side effects and even some deaths.
Humira's updated sales to 2021.
Mate, what kinda of a chart is this? Do you or do you not understand the acceleration of this chart?
The first year they tackled 22 countries achieving some 280 million ...but that isn't AUD... it's USD...the second year I give you $852,000,000 and the third?1.4 Billion. And some of you crazy short termers want a x2 and you are happy? Really, wouldn't you want a decent chunk of shares left for this real fun lift of sales? Wait till we layer up on the indications....
No its not being GREEDY.,..its realising our true potential.
Year 13 to year 14 as an example above, increased by a full 2 Billion USD in incremental sales giving them 16 Billion USD, yeah that's $23.8 Billion AUD. Per annum!
I cant speak for you, but my core is waiting for year 13 in Zilosul sales. Sure we have a few stars to line up... But don't get the champagne out just yet...it took them years...but our trajectory should follow that somewhat, in fact ours could be accelerated...how?
Because we may very well become the only DMOAD on Earth...at least for some time.
Because we are safe...a safety profile that spans some 7 decades....not even one mouse has died due to iPPS.
And because of the PAIN.
Huh?
Yes this last point is one of the most lucrative out there. It has something to do with Off labelling...
ITS ALL ABOUT THE PAINMost patients will give a lot to be rid of the pain, and if you can do it-
- Safely
- With some sense of duration
- And give back functionality
Well it really is going to be quite the standard of care. (My thoughts).
How about some pain related stats
3:
- 1 in 5 US adults experienced chronic pain in 2016.
- Between 11% and 40% of US adults are living with chronic pain.
- Low back pain is the most common type of chronic pain.
- At least 10% of the world’s population is affected by chronic pain.
- Chronic pain costs the US up to $635 billion ever year.
- 191 million opioid prescriptions were dispensed to patients in the US in 2017.
- Up to 85% of patients with chronic pain are affected by severe depression.
But Paradigmers, aren't we forgetting about the off labelling situation. Pain doesn't just mean OA pain.
There are so many patients suffering pain quite outside OA.
Another fact to hammer our potential home:
A full 20% of chronic pain patients who visit a physician receive an opioid prescription, despite research showing it doesn't improve quality of life! 3Can you imagine diverting even a quarter of these patients to us?Some estimates have it at 100 million Americans in pain:
"The Federal Pain Research Strategy recommended development of nonopioid analgesics as a top priority in its strategic plan to address the significant public health crisis and individual burden of chronic pain faced by >100 million Americans".4Another stat from another reference
5:
"The majority of Americans — 58.9 percent of adults — are living with pain. Back pain is the most common type of pain, affecting nearly 2 out of 5 U.S. adults in the last three months, according to the findings from a report released by the National Center for Health Statistics".ARE YOU NEW AROUND HERE?Are you new to Paradigm and HC?Mate you just gotta read the below in full...
This is the document that tells us what we have to combat pain for the very
first time ever . Yes that's right, there is nothing else out there that is non addictive and that is safe and that actually has a high degree of efficacy in reducing pain via NGF secretions from cells in duress.
How strong is Par's concrete base then?
Paradigm set out to answer just two questions in the pain realm:
1) Do bone cells (osteocytes) under the cartilage produce pain mediator NGF?
2) Can our drug reduce the production of NGF by those bone cells?
"The data to that research was subject to peer-review and it has now been published. The answers to the scientific questions are Yes, the bone cells do produce high levels of the pain mediator NGF and Yes, the drug pentosan polysulfate can reduce the production of NGF by those bone cells"....and further...
"The mechanism of action of reducing the production of NGF by PPS is novel".But this exciting story does not end there...merely blocking this NGF is not only not great...but it is a disaster. How do I know this?
By the failed Tanezumab 1.8 Billion dollar deal that was not consummated, because blocking All NGF is a recipe for an immunosuppressant type disaster.
Guys, YOUR Investment's strong foundation is this:
"The reduction of the production of NGF by PPS is not by blocking the NGF (like NGF antibodies) by rather at the mRNA level to reduce the production of NGF by the bone cells thereby reducing the joint pain. This research now clearly elucidates the mechanism by which PPS reduces pain from osteoarthritis".But you know what, its not just restricted to pain from OA.
Its going to be something quite incredible, no not just next year...but certainly year's 5...maybe 10 from now. Yes its not for everyone, not everyone reading this can have patience for years...but for those that can.....Well you know what to do...
Just wait.
Oh and DYOR
- Mozz
REFERENCES1]
https://www.centerforbiosimilars.com/view/house-committee-issues-investigative-report-on-humira-pricing-abbvie-tactics2] https://www.biopharmadive.com/news/humira-abbvie-biosimilar-competition-monopoly/620516/
3]
https://www.thegoodbody.com/chronic-pain-statistics/4] https://journals.lww.com/pain/Abstract/2019/01000/Betulinic_acid,_derived_from_the_desert_lavender.15.aspx
5]
https://www.everydayhealth.com/pain-management/more-than-half-of-americans-live-with-pain-according-to-report/
(20min delay)