B seems solid to get through a Ph3 given it has completed Ph2 with limited side effects. Slight risk that they can't subdue those hypertension reactions, but that in itself would not kill the drug. Its not like it was causing anaphylaxis. Likely would just be approved with a warning to watch out for hypertension during treatment and discontinue use if it occurs (in the worst case). I would say 50/50 that they successfully tame the reaction in Ph2b with the dosing changes, but this is a drug that will make it to market barring the 1 in a million problem that we can't foresee.
P is actually where I think there is the most risk of failure/sub par results given the role of the human immune system in psoraisis and the difficulty of replicating its involvement in a mouse study. Nevertheless, we know that the drug impacts Prins which is a known factor in psoriasis and the fact that the other treatment didn't cure where ours did in the mouse study is encouraging. Overall, I am still highly optimistic that we will have a similar result. Still who knows what can go wrong in terms of determining an effective dose, unforeseen reactions etc. Without the PoC we are flying dark here and its a gamble. These will be the results that will make me sweat.
K will attain a theraputic dose and will be approved. Its toxicity profile is just too favorable to be an issue and the concept of this drug has been proven by the Nutlin Phase 1B study completed in 2012 which also successfully fought leukemia by activating p53 - meaning you can activate p53 to a level that destroys tumors in humans without generating systemic toxicity. Its a golden child that just needs time to grow up. Risk of failure is extremely extremely low.
