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https://twitter.com/Blueberrymgmnt/status/1555630060786384897
The 15 times as much FAP circulating mouse plasma as opposed to human has been mentioned before, but here is a post linking the finding to Prof Bach. Needless to say, if this is shown to be the case with the patients on trial, given the very high specificity of the pre|CISION linker, this could explain the relatively modest dose escalations that Avacta and the investigators have pursued. Because even a low dose is going to exceed significantly the performance seen in animal models.
https://twitter.com/Blueberrymgmnt/status/1555630060786384897
BUMP.
The 15 times as much FAP circulating mouse plasma as opposed to human has been mentioned before, but here is a post linking the finding to Prof Bach. Needless to say, if this is shown to be the case with the patients on trial, given the very high specificity of the pre|CISION linker, this could explain the relatively modest dose escalations that Avacta and the investigators have pursued. Because even a low dose is going to exceed significantly the performance seen in animal models.
UPDATE care of Marty McFly Twitter Additional study quoting higher ratios.
Needless to say, FAP activation in healthy adult tissue should promote more ‘dox-for-your-buck’ accumulating in the TME.
It also suggests non-healthy adults with Arthritis etc. are not exempt from this treatment.
We knew that rodents had higher FAPa levels, but at least I didn't know that it was a factor of 15! (note that the 'higher levels' quoted by Marty McFly was for baboons)
This directly feeds in to 'multiplicative factor' that has been previously discussed, i.e., how much more dox gets to the tumor than standard tissue. In mice it was 18 to 1 (tumour to heart ratio). With 15x less FAPa activity in humans than mice this has the potential to go to astronomical levls, i.e., if everything is linear (which I am sure it isn't, so this is just an example) this could in principle get to 18 * 15 = 270, so 270 to 1 (tumor to heart ratio).
Of course there are two ways for dox to get into the system with AVA6k, either through encountering 'systemtic' FAPa, or through leakage from the TME. I'm not an expert, but based on 1) the very rapid uptake of dox by tissue discussed by Ophidian (suggesting very low leakage levels) and 2) the fact that William Bachovchin's group is looking at the systemic variations of FAPa activitiy between species, leads me to believe that the major pathway of unwanted dox is through cleavage of ava6k from systemic FAPa. This suggests that this multiplicative factor could indeed be much higher for humans than for mice.
Can't wait for those biopsy results!
Great post Timster.
I know its all very exciting - but before too many people get too carried away a couple of important points to note.
Firstly the Form of FAP on the stroma surfaces is different to that free flowing in plasma (that is important when it comes to the ability to snip AVA6000)
and secondly there is a difference between being able to detect something by assay and compare it's concentrations and being able to compare relative activities.
I'll leave it to the Xperts BITL and PL75 to explain and quote the papers
Ophidian
Clip clop clip clop…. In he trounces aboard his steed, name checking as he posts another patronising arrogant deliberately antagonistic paragraph without any provocation at all. Then cries when people point out he’s a twat. What a twat.
Mr pit pony - you are so full of it
Actually it is a pretty good point. Ignorance is bliss I am told.
I simply correct.
I mean, what a colossal bell. Shame you get things wrong so often huh?
but so much less often than others eh ? Clip Clop
Clip clop… hark as he trots off in to the distance, until next time when he does the same thing again… whilst in the meanwhile bleating on twatter about LSE and how much he hates it. What a twat.
so still very good at the insults and extraordinarily poor at explanations, understanding or content then ?
Thank you for the compliment. Otherwise, I simply correct.
Managed to understand what efficacy means yet? Still struggling to use a calendar? Any more price predictions? Any delicious sauce recommendations? Nope? Best trot off to get another filet o fish…
you parade your ignorance like a badge of honour. Humour me - try and give one rudimentary cogent explanation of either of the two points I made at 11:59. I'll even give you some Googling time - ask Rorkes if you need help- he's good on Google, but Wiki probably can't help you with this one you have to look a little deeper and actually understand things a bit
it is simply impossible here to have a conversation about various scenarios because of the personalities who if you ignore the barbs and rudeness, show that the underlying view and need is to shutdown any other view.
The points ophidian raises today are shouted down with pointless previous references to posts that he made of over a year ago. (I am happy to admit I find his tone difficult at times and also have not agreed with all his analysis, however if I felt that strongly about it I would simply filter or ignore. Why do you think these other few never do that?)
For all of you that so enjoy rec'ing these posts at least be aware that you are part of the cancel culture that will not allow any other view to be aired other than their own.
History does not put you in very good company.
Dearest donkey riding oddball, I’ve never posted a single thing about the trial and any of the technicalities. I’ve only ever posted that I’m looking forward to the results and that ever day that passes is a good thing as it continues. Sorry to disappoint you, but I don’t overly care about the technical side of it, I leave that to others, I just enjoy reading about it. However, most posters manage to share their knowledge without needing to try to be smug, patronising or antagonistic, they don’t find a need to be an arrogant twat, they just enjoy sharing and discussing their research. Try getting off your donkey once in a while and not being a twat, you might find you like it.
Yawn, Dacia is here. Discussions are indeed difficult due to the personalities. That was exactly BITLs point, the donkey rider hasn’t ever managed a genuine conversation on here as his precious ego doesn’t allow him to concede when he gets things wrong. The board would be much better off without his attitude and clearly without twats like you - you’re simply a troll poster (with an absolutely atrocious trading record). I only ever respond when he’s being a twat, I can’t help it if that’s 99% of the time. There wasn’t any reason at all for him to name me in his post, only he knows why he did that. Well, other than he’s a twat, obviously.
Ophidian - you’re a charlatan who is more readily exposed. Your ego can’t take any conversation you don’t direct.
I see Marty has you blocked on Twitter.
" There wasn’t any reason at all for him to name me in his post, only he knows why he did that."
03 Aug 2022 17:40
monumentally stupid and that fact you didn't understand why what you were quoting showed your ignorance just makes it really funny.
I have spent hours slowly explaining things on here for the benefit of others certainly not myself and idiots like you try and be clever when clearly you are not it is simply wearing so I now save myself the bother
Don’t bother. You’re a trader, hence the benefit is all yours.
Wow. His lordship seems to be in a dark place and lashing out for no need. Recent posts have been limited to his opinion with no need to have a pop at others and board been all the better for it.
Wonder why he wants to drag it back down and have everyone Neel before him. Look at me don't look at me. Attention seeking of a child.
I'll wait for the standard comments but really hoping someone with all his BTECs can come up with something new even if its not funny. Make my day.
‘monumentally stupid and that fact you didn't understand why what you were quoting showed your ignorance just makes it really funny.’
I quoted the dictionary you utter moron, that’s what was really funny. You were wrong and clearly can’t handle it. Grow up you freak of a man baby. And there you go again… toys out of the pram, ohhh woe is me, I’m not posting anymore, booo hooo, please gather around and beg me not to go. If you change your attitude, then one day you’ll be able to change the record. Look up humility in the dictionary when you finished learning what efficacy means. It’s ok to get things wrong, you’ll be ok sweet pea
He couldn’t admit being wrong the other day.
He was also wrong about the half-life guff on Twitter.
PL: " The board would be much better off without his attitude and clearly without twats like you - you’re simply a troll poster (with an absolutely atrocious trading record). "
" The board would be much better off without his attitude. .." in your opinion..., that's a fairly important caveat, don't you think, or perhaps you recognise arrogance being in fact, your main characteristic? You are never wrong are you.. Oh wait,...LFT, China and its accurate reporting .... (though to be fair your insistence on China being a paragon of honesty was as amusing as it was naive.)
As for my trading record.." Attrocious" you say, well it could be better, but I've done ok here. And thats the trouble for you. You harp on 3 stocks that have nothing to do with this BB, and yet the one stock that you have knowledge of that I have had good success on calling you always ignore, namely AVCT.
You cherry pick info to make false points and to discriminate me and therefore my views.
It can't influence me, because I know exactly what I do. So you can only through your deliberate deceit, be trying to deceive others on this BB.
Or your ego won't allow you to concede how blinkered and ultimately foolish you have been when you decided to wage your war of petty insults on someone who forecasted the likelyhood of the LFT commercially failing when the Stock was over 255p per share.
exactly PL - you quoted the dictionary.