hottod - thanks but you only answered my question in part. FPP...

hottod - thanks but you only answered my question in part. FPP is only CPP rebranded under a different name. KLAKLAK is fine - I read the slide and noted the apostotic property in the excerpt I quoted. The key part of my question in relation to the sequence was - what do the other letters and the items in boxes denote?

andrewk65 - I only know BioExec from his posts on this forum, so can't be sure how reliable his info is or as to his background / experience / credentials / etc. However, from what I have read today it is clear to me that the issue of CPPs interacting with the first cells they come across and the related sink effect is a fairly simplistic characterisation of the problem.

The science has moved ahead quite significantly and there seems to be multiple techniques that have only been discovered in the last 2-3 years (such as PASylation) which are moving things forward in leaps and bounds. It appears (to simplify), there are ways to bind a CPP+cargo to a protein (for example albumin or PAS) and transport it to a target site - in this respect, the CPP-drug fusion is acting very much like a conventional biologic or small molecule drug, so it's really down to the precise recipe(s) that PYC are using.

I want to reiterate my interest in KAI9803 because this was a TAT based intracellular biologic that made into Phase 2b (backed by BMS not Amgen). The drug failed Phase 2b. However, it is not clear to me why it failed. It is important for us to uncover the why, because this trial (I think) has given CPPs a bad name (RH tells me) leading to PYC rebranding their CPPs as FPP. Here is the link to the trial https://clinicaltrials.gov/ct2/show/NCT00785954
and the paper it generated: http://eurheartj.oxfordjournals.org/content/35/37/2516.long

andrewk65 - you may find it interesting that while the paper does mention the danger of generalising animal model studies to humans, it also mentions the cause of failure could be a number of things incl study design and incorrect target site chosen for the drug (this was a bit different being a heart disease as opposed to in cancer there is always a tumour to target).

I take a lot of heart from the fact that the authors speculate as to what would have happened with an even higher dose, as side effects were not an issue and that the there were likely no issues with drug-drug interactions. Given KAI-9803 is a much older formulation from the early 2000s, I think PYC should be much further advanced in its science, just by weight of the sheer amount of advancements that have come about recently.

Today's been a good day for me exploring the science (even though I'm no scientist). Welcome any further insights any of you folks can bring to this particularly given there do seem to be the odd scientist lurking out there.