The Division, determined!

eah I've been following PAR for a number of years. I don't think I need to state how many hours that adds up to over the weeks and months. Currently I have at least 4 different posts I'm slowly working on...I'll get there. But sometimes I have to bump the order of my posts cos something comes up, an interesting article, a pressing topic etc.

Tonight is such a night.

Please do enjoy!



DIVISION

Initially a number of years ago, I was just under the impression that we simply form a case, we chat to the FDA, we devise a protocol and we submit it to the general office of the FDA.



_{FDA - but in actual fact they have heaps of offices across the nation.}



Well a number of years ago I became aware that the FDA is fairly vast and there are specific divisions within this vast structure. I didn't think too much of it until perhaps last year when I realised that we are submitting our application via a division that deals with Pain. But for Disease Modification, it is a separate division, that would be the Rheumatology Department.

So just this week, I finally learnt the exact name of the division we would be filing under. It's called DAAP. This stands for ...

Office of Neuroscience - Division of Anesthesiology, Addiction Medicine, and Pain Medicine (DAAP).

Now while that might be slightly interesting, take a look at what sorts of pain this department deals with:


Acute Pain, e.g.:

• Surgical and procedural pain
• Pain due to trauma/injury
• Pain due to acute inflammatory processes

Chronic pain, e.g.:

• Cancer pain
• Neuropathic pain
• Fibromyalgia
• Osteoarthritis Pain
• Low back pain

The best thing for us is that within this same department, they are charged with a particular area of medicine that has great ramifications for us...



ADDICTION

Along with the Pain division, these guys are across addition, some examples include:

• Nicotine
• Alcohol
• Stimulants
• Opioids

Yes it is the same dudes that also look at the nasties of Opioids for example. I think this is another boon for us, imagine when our P3 data comes back and these guys get a sense of just how good our drug is from an efficacy point of view but also the other side; just how good our drug is from a safety point of view and then, inherently just how good our drug will be as an ALTERNATIVE to the nasties that this dept is so used to having to tackle day after day, after day.





_{The nastiness of opioids...so often totally destructive.}



Two facts for you:






130 Americans die everyday from an opioid overdose, accounting for two thirds of all overdoses.




10.3 million people misused prescription opioids in 2018.







A THIRD PRONG?

Now it's good for us that this department contains these two sub areas which are highly relevant for us. We want a department that tackles positively what our drug can do, ie address pain, but we also want to be in a department that is aware of what we can also do for the negatives out there, ie addiction.

What about a third relevant prong within that very same department?

Yes, this department also handles a future indication for us.

Let me explain. Here is a an extract from their webpage:

"DAAP also regulates the drug product classes that are used in surgical, procedural or ICU settings to provide patient comfort and/or ease of treatment, e.g.: general anesthetics, local anesthetics, dental anesthetics, topical anesthetics, neuromuscular-blocking agents and neuromuscular-blocker reversal agents".


Great Mozz but I don't get the relevance, what's the connection?.

Well it is because of PAR's foresight that they have thought about what iPPS does, How it works and indeed some of the applications in the future. Some " 20% of patients complain of persistent pain" ³ post operatively.

Yes, PAR has a POST Op patent dealing with Pain.

Some of you will know that I love to see the word "Surprising" when reading some of these patents and papers, let me present a paragraph from the patent:


"The present invention is based on the surprising finding that PPS treatment reduces persistent, post-operative pain in a subject following joint arthroplasty".³




MOZZ STORY TIME




Yeah this is always my fave bit.

*Rubbing hands together*...One day I'm going to do these stories as an audio file so you will -hear- my enthusiasm.

This is a real example that occurred in terms of Post Op effect of iPPS. Seat Belts on please, maybe even a shot of one of Violin's Rum (Drink in moderation) - it's a heck of a story.

There was a patient that was suffering from degenerative OA in the left knee with BMEL's and she was suffering from persistent pain following total right knee arthroplasty.



She was 60 years of age and has end stage OA in the right knee and underwent a total knee replacement of that right knee and has "...aseptic, persistent pain from that joint post replacement".

Now, under the TGA SAS program she was treated with a 2x2 dosing of iPPS for just three weeks, not six, just three weeks.,

What happened?



Mate.



"Her left (natural) joint went from Numerical Rating Scale (NRS) pain score of 8/10 to 0/10"

Function?

You bet:


"Lysholm knee function score 58/100 (fair) to 99/100 (excellent)"


Yeah but what about those BMELs Mozz, did the miracle drug do anything for that?


"Pre-treatment MRI (at baseline) showed bone marrow edema lesion size of less than 20 mm. Post-treatment MRS (after PPS) showed bone marrow edema stage to be negligible; minimal bone marrow edema lesion size less than 5mm".


So while her pain in the left knee subsided, due to the systemic nature of the drug, even her right knee experienced an outstanding result:


"Following this singular systemic treatment for osteoarthritis of the left knee, the aseptic, persistent pain in the right artificial joint also subsided/stopped and went to zero".


The observations were clear that it was the drug's effect at work:


"The improved pain response in the right knee was concurrent and immediate in relation to the improvement in the left knee. It was further observed that the improved pain response in the right knee was not consequent to the improvement in the left knee or was it associated with rehabilitation or compensatory to the improvement of the left knee".






In concluding the patent goes on to say

"Surprisingly, the post-operative aseptic, persistent pain in the right artificial knee joint also subsided/stopped and went to zero".



CONCLUSION

It's great that the department we are dealing with at the FDA comprises of three separate areas which are all directly or indirectly highly relevant to us. They are going to be amazed when our P3 data gets dropped onto their desks. I think they will be doing double takes. We already have a few measures that are having incredibly low p values while n has been extremely low (005, n=56 and 008 n = 15).

As a quick example take a look at what one of our new Phase 3 secondaries, PGIC measure was included in 005 and 008, see details also in Appendix A below.


PGIC 005 P = 0.0062 with an n = 56

PGIC 008 P = 0.005 with an n = 15

Can you now just imagine when n = 233 in our P3, what will our P be?



The potential of iPPS is astounding. More new investors will start to understand this in the next few months. I say to a number of pals, we are still at the early stage of this play. It's from now on that it will just get even more interesting...











My thoughts, not to be construed as advice, don't take into consideration only one poster's opinions, your own research is required..






APPENDIX A

005 Program, PGIC was ultra statistically significant:

Much more recently in our 008, n was some 4 times lower than the numbers in 005 but we still attained a very statistically significant result on this one measure:








REFERENCES

1] https://www.fda.gov/about-fda/cder-offices-and-divisions/office-neuroscience-division-anesthesiology-addiction-medicine-and-pain-medicine-daap
2] https://www.maricopacountyattorney.org/396/Opioid-Epidemic
3] https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/11701382
4] https://app.sharelinktechnologies.com/announcement/asx/47595154d6700f1f6761afc6a09c214c
5] https://app.sharelinktechnologies.com/announcement/asx/76393c2170325bd8cd425f9c4d0ffaae
6] https://www.fda.gov/about-fda/jobs-and-training-fda/text-description-map-showing-fda-offices-across-country