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"But the is the point of P1a a safety assessment as opposed to activation? The dose could be tolerable at higher doses but not activating. This study isn’t about getting peoples hopes up."
Just read this - omg what garbage - if it's not activating then there is nothing to be tolerating.
It's like swallowing condoms full of heroine - if they don't burst then no drug so nothing to worry about. You only need to worry about "tolerating" heroine when the things bursts open inside you
just to expand but sorry if this is considered too simplistic.
If AVA6000 is considered to be represented as X-Y-Z//A-B-C-D-E
where X-Y-Z is the linker molecule and A-B-C-D-E is doxorubicin then when FAP cleaves the linker both can be broken down by the bodies usual mechanisms let's imagine that the linker breaks down to X-Y and Z and A-B-C-D-E breaks down to A-B-C & D-E & D & E Simply by measuring how much Z and E is in the blood can tell you how much of the X-Y-Z//A-B-C-D-E has been activated.
Now if you know that there is a concentration of 100 X-Y-Z//A-B-C-D-E per ml to start with and that there is enough systemic FAP to cleave say 5% then you would expect to find 5Z/ml and 5E/ml, so if you are finding 25E/ml then obviously the extra 20E / ml is coming from somewhere - you would also expect to find 25Z / ml too of course for confirmation.
In the same way it may be that A-B-C is excreted in urine and the concentration can be measured and X-Y is excreted in stools and similarly the concentration can be measures and all the data reconciled.
This was meant to help - not intended to insult.
Ophidian
@mowzerrocks - expecting to attract a whole wave of abuse and probably the thread being attacked and taken down - I'll try and answer your question but probably best to copy it and read it at your leisure.
The AVA6000 basically consist of two important elements - the doxorubicin molecule and the linker molecule. Once cleaved both of these two molecules are metabolised by the body and their metabolites are excreted through various routes and can be measured in different samples at different times. Blood levels, urine levels, bile levels, even saliva levels and stool levels.
They know how much they put in because they now the dose given therefore by measuring the metabolite levels on the way out it is possible to work out how much AVA6000 got activated in the body. Because systemic (circulating) FAP levels can be measured before the patient is even dosed, the amount of AVA6000 that could be activated just by "Free" FAP can be worked out and so it is easy maths to then see how much MORE AV6000 is being activated and reasonably conclude that is based on the FAP in the Tumour environment.
You don't have to believe me you can simply Google and learn all about metabolism generally and many many papers on doxorubicin metabolism specifically. The one bi it's harder to track down is the metabolic pathway for the linker molecule but that is also known and being followed (and obviously also reconciled with the doxorubicin metabolites - they should all add up after all).
You might ask why some people work to hard to cast doubt and fear and to rubbish those of us offering the benefit of our knowledge.
Ophidian
what are you so scared of Vegas ? It really is comical the depth your kind will go to - A majority of reasonable readers of these boards just skim your crap seeing it for what it is you have absolutely NOTHING of substance or credence to contribute do you - just ire and abuse. Sorry but you now have to join your pall Wyndum in the bin
some of you live in an alternative universe where I apparently "say" whatever it is you want to interpret what I ACTUALLY say to be.
I have only ever suggested Medusa have manufactured for Tech Transfer not for sale. Similarly I have only ever suggested that the number of components supplied to Mologic is sufficient to equate to LFD manufacture at a certain level.
Keep going if you must but it is both amusing and troubling at the same time. Is it really that dangerous to someone's agenda that it takes a deluge of innuendo and half truth to flood any post I make - bizzare.
Sometimes a gap fill is just a gap fill !
@Goodhunch - I'm not privy to the plans for AffiDX. I have Tweeted on the subject, and to precis that - I expect that we will see a range of AffiDX LFD's for various indications (including perhaps Sars-COV2) in time based on a platform architecture.
@Doctor100 - they were and are just not branded for Meduflow or manufactured for / by Avacta - they are going to low income countries............ as will plenty of other affimer powered LFDs
Ophidian
No I think that is the bottom in now. Gap was closed at 82.4p then just continued down to flirt with the 61.8% Fib retrace off the High.
Upwards now with luck and FDA news cannot be far away. Manufacturing going full steam ahead so there should be revenues too.
Ophidian