Huh? This'll be rich...how are the two connected at all?![https://hotcopper.com.au/data/attachments/3621/3621255-104456e88dbcfd4e91ebc04920dd9f7a.jpg](https://hotcopper.com.au/data/attachments/3621/3621255-104456e88dbcfd4e91ebc04920dd9f7a.jpg)
always wondered why would we rip up a $90 Billion contract with the French for some Nuclear powered Subs from the US/UK? More than that, the new subs are going to be well north of $90 Bill overall cost, let me tell you.
Probably more of a pressing question than the above one is how we at all can draw parallels with this submarine situation and our own iPPS? In tonight's post I shall attempt to answer both of these questions.
Do Enjoy
THE SUBSSo we have to date, spent much time negotiating and working out this all important defence contract and provision of diesel powered subs from the French. In fact it will cost us some money to renege on these contracts and to go ahead with the new submarines, the nuclear powered ones. I always was curious as to why would we do such a thing? Could it be just to bolster our military ties with our old buddies the USA and the UK?
Nope.
There is much more to this story. For that, we need a background in some basic engineering and in fact, some chemistry.
Most old world subs are diesel powered. Mozz, who cares how these things are powered, I get that a submarine's chief duty is to remain clandestine, submerged under the water, stealth-like. Isn't that all we need to care about?
Well actually no. Stay with me on this. So to power all aspects of a sub (think Electrical systems, life support, propulsion and even the ability to surface and submerge via electrically powered tanks to cause floating and sinking alike) we need an adequate power source. This was conventionally achieved by a diesel engine. Now to burn diesel, what is the one most important and vital ingredient required apart from the diesel itself?
Yes, Oxygen.
How much free oxygen is present under the water?
Zero.
So what this means is that these old world subs need to carry oxygen with them in tanks large enough to burn for a number of days. The problem is that the submarines need to occasionally come up for air and replenish these tanks for further burn. The old diesel tech allows for just several days worth of being submerged.
The BIG advantage of nuclear is that no oxygen is required! This now gives the ability of a nuclear submarine a very large advantage over diesel....in theory these subs NEVER have to come up for air. Yes, they can stay submerged indefinitely and in fact for decades, in theory!
Now that's one hell of an advantage.
Sure in practicality you would need to resurface for supplies and to give the crew a break from being under water. But the point is that you can stay under water for much longer hidden from the 'enemy'.
LINK?Yeah got it Mozz...but how is this at all connected with our investment in PAR?
Ahh that's an easy one.
Think of the submarines, at the end of the day, we want the latest technology, we want features that not many others have...in fact in terms of nuclear propulsion it's just a handful of countries that have them....(see Appendix A below). So the link between iPPS and subs is the tech, it's the mechanism of action. It's features that the standard of care simply does not have...we must pay for tech that not many have and thats a fair degree above the current standard of care/application...see where I'm going with this?
Tech involved is full on, single left click to enlarge the above image.2The so called current std of drugs can give back some joint function and pain relief ....but they do not achieve these results safely. There are much higher chances of AE's. There are higher chances of damage to tissues and organs with prolonged use. But perhaps one of the closest links with submarines, iPPS give us a higher level of
durability of the drug.
Just like a nuclear powered submarine have the durability to stay hidden for so much longer, iPPS quite unlike Panadol, Tramadol and the like LASTS much longer.Yes this is subject to the durability and extension studies. Yes others can give pain relief (Opioids and NSAIDS for example) of around 20 to 30% pain relief...what are we? How do we compare? In the SAS program some 89.7% responded with a reduction in joint pain and an incredible 91.7% experienced an improvement in knee function.
"Pain scores reduced over 51.3% and function improved 58.4% (on average) in patients with knee OA".1However, while the above is pretty spectacular, the real nuclear powered capabilities of iPPS (my views) are:
![https://hotcopper.com.au/data/attachments/3621/3621267-4f59794edef3278264d58a3eea347e9b.jpg](https://hotcopper.com.au/data/attachments/3621/3621267-4f59794edef3278264d58a3eea347e9b.jpg)
Durability - Just like the subs gain a much greater durability of staying under the water compared to the current diesel subs, we too will show just how much
longer our positive effect lasts compared to what treatments (lack thereof) are available now.
![https://hotcopper.com.au/data/attachments/3621/3621268-4f59794edef3278264d58a3eea347e9b.jpg](https://hotcopper.com.au/data/attachments/3621/3621268-4f59794edef3278264d58a3eea347e9b.jpg)
A little feature called DMOAD. Keeping the seas patrolled and acting as a deterrent? Keeping OA patrolled and acting as a deterrent for further cartilage destruction and keeping pain
at bay. (Dad humour, who me?)... indeed like the new future subs, we gain the possibility of reversing the course of potential damage.
COSTS?The cost of a submarine program is not cheap. It's not hard to rack up the Billions of dollars when you are talking about such sophisticated machines as submarines, let alone nuclear ones. Then there is maintenance programs of such beasts.It's the same for iPPS...it's the patients that will vote with their feet, demanding that their Docs try a program of iPPS.
There really isn't much to lose if there aren't any chances of serious or multiple AE's. What gives us the confidence of a higher price for our drug?According to an article by Health Affairs
3 an article written by
The Journal of the American Medical Association stated the following 6 criteria are key:
![https://hotcopper.com.au/data/attachments/3621/3621294-11c9a74efe69573353752d29c359b0be.jpg](https://hotcopper.com.au/data/attachments/3621/3621294-11c9a74efe69573353752d29c359b0be.jpg)
How many years does iPPS add to a typical patient? What is a typical age of patient when they acquire the disease? Don't just assume it is an older person's disease, there are plenty of stats that show that OA is increasing at an earlier age. Injuries add to the prevalence. Don't also assume that because OA per se is not fatal it can't be a serious disease. You grinding all exercise to a halt because of onset OA will force you to the surface (sorry, still got subs on my mind). It will force you to stop exercising and this can lead to a whole host of comorbidities. There is plenty of evidence for this.
![https://hotcopper.com.au/data/attachments/3621/3621300-d2675a45e7f91e9c66a594eb840d50bc.jpg](https://hotcopper.com.au/data/attachments/3621/3621300-d2675a45e7f91e9c66a594eb840d50bc.jpg)
A typical new drug's price may be tempered if there is some degree of toxicity or side effects or adverse effects. Lucky for you and I, this is a minimum or negligible in our case. PPS has been shown to be safe over decades.
![https://hotcopper.com.au/data/attachments/3621/3621301-ac48dd982ca0cfdd2d4a6b008341c11e.jpg](https://hotcopper.com.au/data/attachments/3621/3621301-ac48dd982ca0cfdd2d4a6b008341c11e.jpg)
Mate, this is one of the biggest areas for us. I view it as a somewhat of a paradox and have raised it with the company. How, why are the TGA saying that we need to show some advanced benefit with our drug to submit a provisional application? Pain and Function aren't enough? Sure I get that there are other drugs on the market that can give pain relief to an OA sufferer, that can increase the functioning of the joint, but we do these two things SAFELY? Is that not novel?
I guess thats not the point, the point is that they want something not seen before especially in light of a new unapproved drug. DMOAD (Think 008 findings) will show this. Yes we are some time off until this is done and dusted, but it will still most likely beat the final readout timings of our main trials.
Novelty Multiplier? iPPS showing
any scope in the DMOAD arena will be novel and I'm guessing the multiplier in terms of final price will become a reality one day in the future.
![https://hotcopper.com.au/data/attachments/3621/3621306-88bc608a1fe309ad2a1db2235a1a9a42.jpg](https://hotcopper.com.au/data/attachments/3621/3621306-88bc608a1fe309ad2a1db2235a1a9a42.jpg)
Well in terms of time, a lot...also in terms of millions spent so far and still to come. We already have upped the number of participants required in our P3 trials.
![https://hotcopper.com.au/data/attachments/3621/3621308-2d232a34f4e191e8cc0dc3c46df17064.jpg](https://hotcopper.com.au/data/attachments/3621/3621308-2d232a34f4e191e8cc0dc3c46df17064.jpg)
Another banner I think we have covered, no other drug can do what we do safely and with the durability. The best thing is that look at all the current pain drugs, each and every one has major drawbacks. We truly will be novel not just in the OA space (My views, subject to trial confirmation)...as my friend
@Ave Maria used to remind me, Mozz, there is a -lot- of inflammatory conditions we could just address one day.
![https://hotcopper.com.au/data/attachments/3621/3621311-394d93a71282b01925ef50faf34c75c1.jpg](https://hotcopper.com.au/data/attachments/3621/3621311-394d93a71282b01925ef50faf34c75c1.jpg)
What this means is TAM....are you new to us? Read this one to get a better sense of what is TAM and how it applies to us...
(Single left click on the below hyperlink) :
TAMWRAPThere are some big dollars being bantered around but when you have such a large geographical country to protect, it ain't going to be cheap. We are an island so the protections of our sovereign waters is important. If we are to spend upwards of X Billions, you might as well get the best. In the same light, If I'm in pain, if I have a destructive disease thats only going to eat at my joints more and more over time, I want something that works, something that is safe and something that
lasts.
I don't want a band aid that last a few hours, that has terrible side effects over the longer term, thats potential additive or destructive and that will eventually lead to surgery. If there's a chance that iPPS can do wonders for me AND there is little to NO downside if it doesn't work, I'm in...if it costs me, so be it, but you know what, insurance and the Government are there as a safety net. They too will one day realise what the data set is saying and the stats involved and they will come to the party to save themselves the real dollars of surgery and patient vexation, it could really save them Billions over time.
DYOR and here's to a ...err...well,
buoyant week.
APPENDIX A
REFERENCES1] Baker Young Research 24th February. 2021. Pg. 12
2] https://www.navalnews.com/naval-news/2021/07/us-navys-virginia-class-submarines-get-more-tomahawk-missiles/#prettyPhoto/0/
3]
https://www.healthaffairs.org/do/10.1377/hblog20160328.054162/full/