I have to respond to this one...my comments in red...but first...

I have to respond to this one...my comments in red...but first know that I admit there ARE risks, a lot of legitimate ones...we are an infant in our journey still, we have no official revenue, granted.


Right...let's go:

KNOWN RISKS

1. Clinical Trial Risk - e.g. FDA very unlikely to buy the repurposed idea because existing on market PPS products are oral with different formulations and different mechanisms of action, so to FDA, Zilosul is a new product.

2. Financial Risk - Agree, definitely a $ shortfall already and any further FDA asks will cost more time and more $ millions. Expect big discount in next capital-raise, probably within 12 months.

3. Time Overruns - always happens in late stage trials, always. P3 will be lucky to complete '25 and must add then minimum 6 - 12 months for reg. evaluation and hope nothing further is required. As data on severe OA seems to have been excised from the P2, to establish the minimum effective dose could easily require two, or maybe even 3 dose-ranging studies - all would add time and cost.

4. Personnel Risk - PR hasn't engaged genuine internationally recognized OA leaders so far, getting a bit late

5. Market Risk - big risk when instos head for the door; sooner or later they will and sooner more likely if they get nervous.

UNKNOWN RISKS

1. End Product Labeling - DMOAD claim is heroic; generally requires absolute min. 2 years compelling data vs placebo. P2 Disease modifying is data very weak, at best - big stretch to claim any meaningful DMOAD in P2.

2. Key Man Risk - PR's new team is VERY inexperienced, desperate need for world class OA expertise. PR can't do it all himself.

3. Regulatory Risk - FDA required shift from Mild/Moderate to Moderate/Severe for P3 - Severe OA is a very tough hurdle, will need much, much better data than P2.

4. Corporate Action - Don't know about PR's health, but licensing or M&A at this stage would clearly not support the current Mkt Cap. Would shareholders support big takeover discount?

5. Commercial Approvals - Big pharma will want robust head-on comparative data which P3 does not provide at all. How will PPS fair against Opioids, NSAIDs, Steroids, etc. in the pain market? Anybody's guess?

6. Stakeholders/Competitors - Existing equivalent or better pain relievers already entrenched in world markets at much lower price, some with powerful marketing & much lower prices -+ $2,500 seems fairyland

KNOWN RISKS

1. Clinical Trial Risk - e.g. FDA very unlikely to buy the repurposed idea because existing on market PPS products are oral with different formulations and different mechanisms of action, so to FDA, Zilosul is a new product.

What do you mean the FDA are very unlikely to buy the repurposed idea? They are about to issue us an IND....they have already given us POSITIVE feedback from a type C? Err... we already have clearance for an IND through EMA??? This happened months ago.





2. Financial Risk - Agree, definitely a $ shortfall already and any further FDA asks will cost more time and more $ millions. Expect big discount in next capital-raise, probably within 12 months.

Yes you are right, there is risk here, not arguing this one, but I am saying just as there is risk in this area, there is also a chance we might score a deal before we need a solid injection of cash. There are other non dilutive ways to fund a shortfall...But your point taken...there is always a chance of this happeneing.



3. Time Overruns - always happens in late stage trials, always. P3 will be lucky to complete '25 and must add then minimum 6 - 12 months for reg. evaluation and hope nothing further is required. As data on severe OA seems to have been excised from the P2, to establish the minimum effective dose could easily require two, or maybe even 3 dose-ranging studies - all would add time and cost.


Again, I cant argue too much here, time over runs are a real risk specially in terms of Covid and Covid new strains and the situation in USA and much of Europe. There is no doubt risk here of time over-runs. yes there is also mitigation of this via de centralised clinics, spreading out of the same, multiple sites , nurses going to patients to avoid disruption and of course vaccine roll outs by the time we get to the bulk of recruitment..but yes, there is risk.


4. Personnel Risk - PR hasn't engaged genuine internationally recognized OA leaders so far, getting a bit late

This is rubbish.
Dr Felson, world renowned authority on OA...look up his credentials (Thanks Denial - see his post), he has more peer reviewed published articles than anyone else I can find in the OA space..he has equal credentials in the RA space...who could have better credentials in booth of these areas? Where did he get his qualifications from?

MD John Hopkins University MPH Boston University School of Public Health and to top it off,AB degree (cum laude) (this means with distinction) at none other than, you guessed it, Harvard.
...What about Dr Donna Skerrett, how many times has she been to the FDA with a drug for IND? 30 years of industry experience. Who can you suggest has more experience in this role?

Dr Ravi - Peer reviewed doc for MOA of iPPS. Super credentials.

I could go on with other seniorstaff and recent appointments...I'd need more pages here at HC.


5. Market Risk - big risk when instos head for the door; sooner or later they will and sooner more likely if they get nervous.

True if it happens, cant see it happening, no need for them to get nervous, they will be fighting themselves over shares once they realise what we have and how serious we are.




UNKNOWN RISKS

1. End Product Labeling - DMOAD claim is heroic; generally requires absolute min. 2 years compelling data vs placebo. P2 Disease modifying is data very weak, at best - big stretch to claim any meaningful DMOAD in P2.

Hmm not sure why you deem it to be weak, what are you comparing it to....Nothing....zero...there is no other DMOAD...it wouldn't matter if we show just a 3% improvement, its already infinitely more than anything else...(zero).

This is objective data:


How is the above weak? I can clearly see (and Im not even employed as a Radiographer) that the Blue circle is smaller and both pics are to scale in case you were thinking of counter arguing?...(Thanks@Hrdwk for reminder of this pic)
A regression of BML...want more? plenty...check out the same effect in the RRV data, 'Near remission' is key here...








Another example...


Placebo goes up (gets worse)...iPPS data goes down...this is DMOAD evidence...this aint weak data. look at the difference in %'s



Wait till you get 008 data (my views)


2. Key Man Risk - PR's new team is VERY inexperienced, desperate need for world class OA expertise. PR can't do it all himself.


Refer to Point 4) above
True, PR cant do it all himself, that's why they are recruiting, look at all the staff appointments just in last 12 months.




3. Regulatory Risk - FDA required shift from Mild/Moderate to Moderate/Severe for P3 - Severe OA is a very tough hurdle, will need much, much better data than P2.

Completely wrong..we had severe cases in our P2B..also in our recent EAP, in fact most of the candidates in this program. In fact severe will be great for us...they still experience a % decrease in pain and increase in functionality...

Check this one out...here is your KL 4 even they get a reduction in end points (see overlap in red circles...its all green here, right through the grades)
:






4. Corporate Action - Don't know about PR's health, but licensing or M&A at this stage would clearly not support the current Mkt Cap. Would shareholders support big takeover discount?

No they wouldn't, hopefully they won't have to.

5. Commercial Approvals - Big pharma will want robust head-on comparative data which P3 does not provide at all. How will PPS fair against Opioids, NSAIDs, Steroids, etc. in the pain market? Anybody's guess?


Plenty of evidence of how destructive Opioids and NSAIDS are and how they compare to iPPS.
We have already seen pain reduction in clinical settings...Some 50% achieved 50% reduction in pain, some 75% achieved 25%...these figs are much better than any Opioid and without the addictiveness and other side effects...! tell ya what, bring us evidence of how Opioids and Steroids and even NSAID's are better than us, you can't there is a world wide push against them and to limit them. None of these are designed or meant to be long term OA pain limiting drugs/solutions, they are too destructive and nasty.

Example - Tramadol, must be taken daily...can lead to addition and substance abuse, read this article:

https://www.altamirarecovery.com/blog/long-term-effects-tramadol-addiction-can-treatment-prevent/

iPPS is non addictive.



6. Stakeholders/Competitors - Existing equivalent or better pain relievers already entrenched in world markets at much lower price, some with powerful marketing & much lower prices -+ $2,500 seems fairyland


Yep, you are dead right, lower price for a reason as they are SH&t not very good. You can't take these lower quality std. of care all of the rest of your days....you will end up with grade 4 and then TKA in most cases....if not possible liver and kidney failure and or addition before that

Regardless of marketing spends...when the word finally gets out that we offer more pain relief, increased joint functionality...safer and a chance at reversing or halting the underlying progression of cartilage destruction...it will take on a persona of its own.






All my views but based on science....
Don't take me as being too invested or too biased or even too defensive, I still gladly and publicly admit, we are NOT risk free, some risks are real and could occur. Never rely on one investment no matter what research anyone does.