Replies to post #232985 on Innovation Pharmaceuticals Inc (IPIX)

[Jhawker]

Thanks for your insights! Very well reasoned and articulated!

[slcimmuno]

Thx Biodoc - great insight and agree there will be lots of data to mine in the PRU study beyond the PASI 75 scores ...

If PRU delivers (successful trial), in Combo w BTD for BRI-OM and d/Deals in those “double-digits millions”, then major Green Pastures and Blue Skies

Think if we have 2 partnered Ph 3s (OM, PsO) - to the moon

And I really want to see what Kev Oral and Bri Derm can do

In about 3 months should have a very clear picture

[Echo20]

Biodoc

Dr. Menon tweeked P to new potentials. These formulas and outcomes are due to the research and calculations of Dr. Menon. If successful his credits will be elevated to stardom.


Echo 20

[frrol]

Good point on the Pruritis, bio. And if (here's hoping) AEs are not a big issue then the 502b2 pathway is gpnna be a big help. Let's see.

[To infinity and beyond!]

Your own post is circular, so no need to argue

Showing signs of benefit is a great deal different than high likelihood of success

Nothing more needs to be said- other than we all benefit from your insights

[To infinity and beyond!]

5052b: as you note, Ziagen is not Prurisol. How can the pathway then apply? As you note, different metabolism , different mechanism of action, different drugs. That pathway may not be so easily won. Even though touted as an advantage by the company

[To infinity and beyond!]

Science versus faith: inability to support bold letter conclusions. Evidence based medicine versus faith-based hopes.

We will begin with science. As of this warm New England morning, we can all agree on your points that P2a had some signs of benefit at 100 mg BID. We can also all agree that 150 or 200 BID may have more or less efficacy. Here on out is an unknown, and the mouse data were not repeated in P2a.

Then you veer into sheer faith with bold letters stating high likelihood of success for P2b. There is no factual basis for such hopes. Certainly none is provided by you, which makes sense, since such facts do not exist. P2b may provide them, and the curtain will shortly be pulled to the side.

But your bold letter conclusions are not based on facts but faith and hope.

[PlentyParanoid]

Biodoc, sorry late comment. I did not notice your post before today.

"Is it possible that 100 mg bid is the maximum effect and further increases in dosage yields no further benefit. Of course it's possible but I believe this is unlikely"

I would say more than unlikely. We have preclinical lab results that show the following: prurisol 10 mg/kg BID outperforms prurisol 10 mg/kg QD which, in turn, outperforms a massive dose of methotrexate.

On napkin calc:
Known:
1. 10 mg/kg is roughly equivalent to single 800 mg pill assuming 80 kg (175 lbs) average weight
2. Prurisol's half life in human plasma is about 2 hours according to IPIX.
A reasonable assumption:
3. Therapeutic threshold for prurisol is somewhat above the max plasma concentration resulting from 50 mg pill.
It follows approximately:
1. Plasma concentration from 800 mg QD stays above the therapeutic threshold for about 8 hours each day.
2. Plasma concentration from 100 mg BID stays above the therapeutic threshold for about 2 x 2 = 4 hours each day.
3. Plasma concentration from 150 mg BID stays above the therapeutic threshold for about 2 x 3 = 6 hours each day.
4. Plasma concentration from 200 mg BID stays above the therapeutic threshold for about 2 x 4 = 8 hours each day.

One way of looking the above calculation is to say that in prurisol p2b trial 200 mg BID dose should be about as efficient as 10 mg/kg single dose from the preclinical tests. 150 mg BID should fall somewhat short of 10 mg/kg results, but still do better than 100 mg BID dose from phase 2a trial. Plus this: it is very likely that 200 mg BID is not the ceiling for efficacy - we still have that 10 mg/kg BID outperforming 10 mg/kg QD in preclinical. However, toxicity may become a problem before 10 mg/kg BID dose level. All I can glean about AEs vs dose is from guidelines for abacavir: recommended daily limit no more than 600 mg.

Obviously interpretation of pre-clinical results should always be taken with a good dose of scepticism. Also, I may have gotten something wrong. Care to comment?