The Humira comparative, and how about a bonus?

here simply is not enough time in my day and night to write all I want about PAR and iPPS in terms of all the research I'm reading about when it comes to OA and the amazing action of iPPS. These posts are merely but samplers, small tastes of what the real research is uncovering. The peer reviewed articles in some of my included references in these posts are incredible reads and together form a very strong case for us going forward (my interpretations).

I'm deliberately avoiding the real heavy science so my posts are readable. I also must acknowledge some of my sources but they want to stay anonymous and HC is anonymous, you know who you are, your incredible insightfulness and constant chats are invaluable, you have enabled and encouraged me to continue here for the greater good - us shareholders, I am also a humble beneficiary.



Tonight, lets chat about Humira.

But no, it wont just be a rehash of some other drug, some other story...I make this relevant to you and me...I give you what their story was but I compare it to ours. Its a Mozz^© post so there are bound to be some bonuses along the way...

I trust you will enjoy...





HUMIRA - Humble beginnings

Originally a joint venture between Cambridge Antibody Technology and BASF in the UK, Humira's brand name is a drug called D2E7, adalimumab.

It was in the year 2000 that Abbott acquired the pharmaceutical component of the German chemical company (BASF) for some $6.9 bn.

"Abbott at that time was highly criticised by many investment banks for not having any blockbuster drugs in their pipeline. Abbott’s hope was that D2E7 would be the needed blockbuster".


So here we have a situation where the taking over company was hoping that there would be a blockbuster out of this and they still paid $6.9 Billion????

Humira was approved on day 1 of 2002.



LAYERING - The Revenue Cake




_{Yes please...}


I love cake, I don't eat a lot of it...but I will have some here and there on special occasions, love the icing on top...but in moderation! In the same way Humira eventually had multi layers of revenue....that's a clue for you and I. Its so easy to take an investment, be patient for a few years and get out at an X3...an X4....but I have learnt from that in the past.

In cases like PAR, yes it is prudent to take some cash off the table when your cost of capital is covered. Its a great idea to crystallise some profits...but unless and until something really drastic happens, a big shift in plans to the negative, a huge change in management, personally I ain't going to be selling too much too early. I want to still have a meaningful position in 10 years form now...I still want to have a good holding in 15 years from now. Its the long term that looks the absolute brightest, the tastiest for me. As Scott Williams said, show me the dividends.

Humira started off with just one indication, Rheumatoid Arthritis. It then started layering as more R&D was conducted.Psoriatic Arthritis in 2005. Chron's Disease was added in 2007.

But layering doesn't just mean one set price and you are done...

“When the price of the drug is high to start with and then increased incrementally twice per year, year on year, the revenues skyrocket”.

Its the life-cycle management that has been instrumental in Humira's success. It could be the same for us.

But this Mozz report isn't just a recital of some news you can get off the internet. Nah, lets just make this personal to us.

We are starting at such a better base compared to Humira, one of the best selling drugs of all time.



HOW?

How is our starting base any better than one of the world's best selling drugs???


1) We have two indications, sure OA is much larger than MPS...but MPS is large on its own....yep there ain't many patients...but the charge per patient is going to be well north of $2500 or $6500.

2) Safety Profile, I'll chat more about this further below in this post...but its this area that is one of the most important

3) Market Size. No point in having a world beater of a drug that's hands down better than anything out there if the market is teeny weeny. OA is TEN TIMES THE SIZE OF RA.... Yeah what about the Pain market, how big is that then?
If you are new to us, welcome. iPPS can also reduce not just OA pain....but any pain (subject to trials).

4) Mate, as if the above isn't enough, what about how comprehensive is our P3. Whadd'ya mean Mozz, isn't it just 002 (Main trial) and 003 (Confirmatory). Err no...what about:

• 008 Synovium
• 010 Hip
• Durational
• Retreatment
• Rescue observations

5) DMOAD (Subject to trials)..yes Humira is a DMARD...but it certainly isn't a DMOAD. There is NO DMOAD.
This is what the world wants....you do this safely and its a game changer...I don't even know any game that's comparable.




THE NEGATIVES OF HUMIRA - It's not the be all end all for everyone

Humira is one of the best selling drugs in the world. This does not mean it is the safest.

Finally what is Humira? It is a drug called adalimumab . What is this? Its known as a immunosuppressive. This essentially means that the drug binds to TNF and blocks it.Yeah sure the advantage is a meaningful pain reduction, but there is risk.

There is a risk that by fully blocking TNF you aren't allowing the body to fight against foreign bodies. This can increase the risk of infections. there is even a higher chance of bacterial infection and there have been deaths linked to this drug.


The other risk here is that in some patients, the chance of cancer may be increased. A rare cancer called hepatosplenic T-cell lymphoma can also be associated with the usage of Humira in some cases.


"Specifically, patients taking TNF blockers have developed lymphoma, skin cancer (including basal cell and squamous cell) and leukaemia". ³



_{These are some of the choices some RA patients face.}



You guys want another example....how about this one:








Yeah yeah Mozz, what's your point....my point is that one of the worlds largest selling drugs isn't all that safe for each and everyone.⁴


If you delve just under the surface, there are reports of serious AE's.⁵






So much so that the FDA have slapped a Black Label warning on Humira. Not only this but I found out a few months ago that if you are on the drug you are highly recommended to actually carry a card to that effect, just in case:

This is not a drug to used without real thought on possible ramifications.

One of the main reasons we are excited about PAR's iPPS is of the great safety profile. As a patients, as a Doc, its no doubt the number one consideration. No point in having a great drug that has all the efficacy if you are just transferring the risk...transferring the possible danger.


EFFICACY

Apart from safety, the next question then is how well the drug works? We really talk in averages here as some people will even respond well to placebo...we want to know how the average performs so we can have a comparator. We already have good data on Humira...lets take a look at how they generally perform:

"Ultimately, the study showed that 40% of patients taking HUMIRA achieved and maintained remission at 26 weeks,^* and 36% of those patients achieved and maintained remission at 56 weeks. Individual results may vary. *Compared to 17% taking placebo". ³


We can now compare this to what our patients experienced over a similar duration.

While we don't quite know about remission in terms of OA (We should get an idea of at least durability and potential 'remission' specifically in OA/Synovial observation soon) ...we can at least compare our 56 days result in a good sample of patients:



But in actuality, we do have some remission clues, it occurred in our study of RRV.





Mate, the remission word is a real clue, yeah? 61.5% experienced near remission!


Yeah Mozz, while you are on this theme of clues, I don't suppose you can you give us any further insight on those upcoming bio markers??

Mate.


BONUS TIME

Dang it man, you know I like bonuses, those wonderful out of the blue surprises.

Like the one that we are recruiting in Canada - that does things for me. Canada is a whole new area where I wasn't expecting any recruitment.

Why does this matter, cos when we get that incredible news one day (my view) that we are a GO...the Canadian authorities will already have their own data that their Authority has seen for themselves, its immediate accreditive sales potential in an entire new country.

Hmm... Wouldn't it be just so good if I could shine some sorta rough predictive light on what we MIGHT see at the end of September? (Spec statement, please do your own research, don't rely on just one enthusiastic poster).

How about this for a statement, I think you should read the entire paragraph, I nearly choked on my afternoon chai when I re-read this earlier today.




My ears perk up when I hear the words "bone integrity...was increased". I cant speak for you...but I want my bone integrity to be up there!


Jeepers Mozz, where the heck did you get that above?

Yep, that was from an OFFICIAL PAR announcement back in Feb 2021.

The one that excites me the most is that CTX-II...its been deemed to be one of the best prognostic OA biomarkers there is ! Nah, its not just me saying that, its our friends at OARSI.

It's those guys that specialise in investigating possible OA diagnostic biomarkers, ramifications for us? You would think so!



Yeah yeah Mozz, love all the theory mate, love how all the words point to us being superstars, can't you give us some hard core numbers?


Gee you guys don't want much do you?

This one also made me kinda drop my jaw and immediately ring a few close mates to ask them if I was dreaming....Yeah I even called a broker that specialises in bio pharma's, even he didn't know about it and went straight to Dr Mukesh's presentation to verify for himself.

Again I'd ask, who knows about this..? That guy in the doc surgery complaining about pain? The nurses in the hospital? The orthopaedic surgeon, the rheumatologists, do they know what iPPS is? What about those 20 or so Geriatric specialists that I personally asked when my dad was in rehab after a heart scare? Nope, not ONE had heard of iPPS and what it can do for OA. Let me just assure you now, the potential, in my view only, is off the chart. I don't really care how many shares you own...do me (and more importantly yourself) a favour...have some shares (I call it the 'core') that you hold for the super long term. (Not at all advice, you must determine if this is the right strategy for you, imagine it all goes to zero, where would you stand?).


Do they know the potential efficacy for the only remaining unaddressed HUGE disease in the world?

This is going to change one day, we will really surface in my personal view.


Hey you reading this, did you know you are still early to the party?







You know what the above is saying to you right? Going from a Grade 3 to a Grade 2 OA isn't possible based on any current drug in such a short duration of time.

Right then, let me show you why my jaw dropped a number of weeks ago:



COMP and CTX II have both been identified as good prognostic bio markers. This was the first time I had seen CTX II, I nearly thought it was a slip up... I'd be happy if the CTXII levels fell and Placebo fell only by say 10%....for Placebo to go UP is a distinct advantage for us.
This one single chart was enough for me to increase my personal holding. (Not at all advice, spec statement, just because I believe in something should not influence you).


WHAT DO WE NEED?


Why bring up Humira and why re-state our observations?

I do this to draw parallels so you can see the place we may be heading to.
I do this so you can see the value
I do this so we can ALL see the nexus...between what's out there...and what we may become one day.

Here is a peer reviewed quote:

"Various disease-modifying treatments have been studied for osteoarthritis and, to date, none has achieved US Food and Drug Administration (FDA) approval as DMOADs". ⁶


What do we need to show?


"At present, DMOAD development must demonstrate slowing of radiographic JSN that is ‘clinically meaningful’ – that is, will be associated with improvement in symptoms or function ".


Guys. JSW (Joint Space Width) is also an observable we are exploring, one of the structural bio markers. Yes we do need to fulfil our primary endpoint in a clinical setting...but what an elixir, what an accelerant its going to be when we present our findings from a biomarker point of view.

Oh to be a Fly (Mozzie?) on the wall.




To reiterate, see how smart PAR are...they are not just satisfied with one bio marker, or even a handful. They want adequate representation over ALL the BIPEDS.



Mozz Speak^®


WHAT IS A BIPED?

Its a Bio Marker for OA classification...


Burden of disease
Investigative
Prognostic
Efficacy of intervention
Diagnostic
Safety

A good company with a prospective drug in OA would love to have one of those groups covered....how many groups do we have covered?

The teach. has asked us for one...we give them at least one from all groups! I love it. This is so my company...doing so much more than the basic requirements...




Yeah the above is great...BUT I want more...


PAR have also added into the all important Phase three:

"... other measures of MRI worsening (e.g. bone marrow lesions), symptoms documented by patient questionnaires [e.g. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS)]..."


Yup..I'm talking BML size....grade....volume...area.



CONCLUSION

The story of Humira is insightful for us...we saw an amazing pathway to success despite the drug while being good, did have and does have a number of risks. Our product, if successful in a P3, has wide ranging ramifications in terms of addressing inflammatory responses, particularly in a chronicle sense. OA is massive, just a small slice of the market will translate into Billions potentially...the future indications could be many and far reaching.

Yes we need time...but this story is unfolding week by week.

Humira attainted some $20 Billion USD in a single year. Yes I know it was some 18 plus years from inception...but it isn't a completely safe drug...it is a drug in a market that's just one tenth our size and that's only OA -v- RA...you include pain and a myriad of other inflammatory conditions (Yes @avemaria I remember you)....well you see where I'm going...






Just exactly how far are we really away from greatness?







- Mozz







REFERENCES

1] https://www.medicalnewstoday.com/articles/dmards-vs-biologics-rheumatoid-arthritis
2] https://www.humira.com/ulcerative-colitis/transcripts/how-humira-works-video-transcript#:~:text=HUMIRA%20is%20a%20medication%20called,Crohn's%20disease%20or%20ulcerative%20colitis.
3] https://www.drugwatch.com/humira/warnings/
4] https://davidhealy.org/stacy-london-what-not-to-take/5] https://www.drugwatch.com/humira/warnings/6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694600/
7] https://www.sciencedirect.com/science/article/pii/S1063458406001038#:~:text=Results,for%20use%20in%20OA%20investigations.