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He will never need to persuade an II to part with cash again
ahem... in my opinion
p.s. - how many would howl like crazy if assets were sold under their real value ?
I could sell the woods or the irons or the bag separately (having eager buys for each) if I had to should the need to pay a part payment for my golf tour come up......... but selling them all together would likely get me a better price - when the time came that I needed to sell
If you had booked yourself a golf holiday and your plan to finance it was to sell an old set of clubs and an old bag - then, if the date you actually needed to have the money in your account by was well enough in the future and every time you put the wood, irons and bag up on ebay you got offers exceeding what you needed and bigger than the last time you put them up on ebay...................... Why would you rush to "do a deal" when you knew the value of your assets for sale was only going up and the point at which you needed the money was still well in the future?
Just asking as I'm thinking about a golf tour.
I gave up sharing anything I thought useful on here a long time ago due to the rudeness and insults of some that is just beyond reasonable.
However – after today and with the unabating nonsense being spread to try and sew fear and misinformation, I thought I would share something I wrote at the start of the year for a different forum as I think it might help some people with understanding the monumental truths present on slide 15 of todays slide pack
You may have heard of ADME studies – this is basic pharmacology and it stands for Absorption-Distribution-Metabolism-Excretion
Absorption is how a drug gets into the bloodstream
Distribution is how it moves out of the bloodstream and into other tissues
Metabolism is biotransformation of a drug by organs or tissues (primarily the liver, kidney, skin or digestive tract) so that the drug can be excreted. To facilitate removal via feces or urine, the drug compound is altered to become more water-soluble.
Excretion is the process by which the metabolized drug compound is eliminated from the body and through which routes.
First off a little bit of terminology for us:
Distribution half life: the amount of time required for the plasma concentration to decline by 50% during the distribution phase.
(Doxorubicin – 5 minutes)
Elimination half life: the amount of time required for the plasma concentration to decline by 50% during the elimination phase.
(Doxorubicin – 60 minutes)
Terminal half life: the amount of time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose.
(Doxorubicin – 30 hours)
Errrrrr – hang on wtf 1 hour vs 30 hours – what’s going on here ? Well initially drug moves from the blood stream into organs where it is stored up and/or metabolised, but as the plasma concentration declines and the organ concentration grows – eventually the process goes the other way and drug starts to travel back into the bloodstream from the organs.
Now….. (this is where it gets a bit more complicated) – All these data on the triphasic plasma decay of doxorubicin are based on dosing doxorubicin intravenously. Remember ADME ? well the A is a done deal here as it is simply squirted straight into the blood stream by IV.
Because AVA6000 is the drug we are actually dosing to our patients, it is TOTALLY different. Because the doxorubicin is only cleaved in the presence of FAP there can be only two processes I can think of that will get doxorubicin into the bloodstream – Firstly, any free FAP which is systemically circulating can cleave AVA6000 liberating doxorubicin and secondly any doxorubicin which is cleaved in the TME but NOT immediately intercalated into a cancer cell and is somehow (I have no idea how but it will certainly need to be concentration mediated) liberated into the bloodstream.
this process should intuitively say to you that the plasma concentrations achieved initially by our newly modified “a” absorption process in our adme model are very very small compared to the bolus “a” process of squirting it in by iv. [this was proved out today on the graph on slide 15]
dr smith kindly shared some plasma concentrations of doxorubicin with us at science day if you recall and they were pretty small and also (importantly) showed a nice dose dependency compared to the dosed ava6000 levels.
right – just for a moment let’s ignore what’s happening in the tumour and concentrate on the blood plasma concentrations of doxorubicin.
we’ve done the “a” of adme – it’s in the blood, so now lets look at “d” distribution
we know the distribution half life (5 mins) so we can pretty much say that it is being taken up by other tissues almost immediately. we know from a plethora of studies that half of it ends up in fatty tissues – the other half goes into the heart, liver, kidneys etc. and once it gets there we need to look at what happens next. “m” metabolism.
the big problem with doxorubicin is not the drug itself per se but the primary metabolite that it is broken down into and this is a secondary alcohol called doxorubicinol. it is the doxorubicinol that has very high cardiotoxicity and is what kills heart cells and causes the problem. it is the accumulation of doxorubicinol which underlies the imposition of a lifetime limit for administration of doxorubicin.
still with me ? right here’s where it starts getting good. lets think about the “e” elimination. the body is very good at getting rid of stuff – it does it all the time. typically things are excreted either through the skin (in sweat – think about how you smell after a particularly garlicy spag bol), through urine (some may be able to smell after you’ve eaten asparagus – but that is another interesting genetic conversation for another day) or through faeces. and this is how both doxorubicin and doxorubicinol are removed from the body (also ava6000 but that is not pertinent yet).
the body – as i said is very good at getting rid of stuff but not necessarily when it is overwhelmed. if you were to drink half a pint of beer every half an hour you would be waiting a very long time to get ****ed, but if you quaffed 6 pints in an hour you would probably (as well as feeling pretty rough) be well ****ed. this is because a typical person can metabolise about one unit of alcohol per hour at a steady state.
it's exactly the same for drugs – the body can metabolise away most drugs quite reliably at a steady state but can be overwhelmed by concentrations.
Here is the thing – the rate at which doxorubicinol can be removed from the body is very sensitive to concentration. In studies on doxorubicin where the same amount of doxorubicin was administered all in one go (bolus injection) versus over an hour (IV injection) showed that doxorubicinol was removed FIVE times better for prolonged IV administration rather than for bolus injection. Now this is critical for limiting the cardiotoxicity clearly.
For straight doxorubicin however – we have a problem. Slowly slowly dosing the doxorubicin means that we can’t achieve a high enough concentration to be able to actually hit some cancer cells – or at least enough cancer cells to make it worthwhile (remember how quickly doxorubicin is taken up by the body ?) but if we give higher concentrations of doxorubicin so we can have a meaningful effect at killing cancer cells then we overwhelm the bodies elimination process and allow doxorubicinol to build up in the heart and cause the cardiotoxicity.
Getting it………? AVA6000 is like giving the bolus injection of doxorubicin but straight into the TME because that is the pretty much only place it gets released but is like giving the sustained slow IV doxorubicin into Plasma because that is how it is absorbed as doxorubicin after AVA6000 administration.
So….. I have said almost from day one that for me the obvious way to go here is lower for longer – keeps dosing AVA6000 at levels which can be comparable to fairly high dose straight doxorubicin to benefit from the ongoing cell killing whist avoiding the toxic build up of heart killing doxorubicinol.
Todays update was superb in it's messaging in my view and short term share price fluctuations are just an inconvenience. The science is sold, the platform is proved and a new paradigm for cancer treatment is on the horizon.
You really can't read can you ? politeness is reserved for polite people you deserve none you are an abomination of a person.
Todays presentation gave us remarkably brilliant insights to the future of cancer care and to what this company will enjoy going forward. You just want to foul everything for everyone you are vile.
The platform works (superbly) patients will live longer and better lives and the opportunity exists to use even more potent cytotoxic compounds for even better outcomes. What oh what is not to like ?
I gave up talking to you and tried to rely on the fact the whole world can see you for what you are - I lapsed and I will now return to that position again. No one by no one of even moderate intellect could fail to see the tissue of lies you try and present
"That'll be the initial ratios Ophidian as per the logarithmic scale?
But the total exposure?
The Area Under the Curve?"
I thought you said you could read ? it's at 24 hours not time zero you utter utter plank read the slides and try just for once to actually interpret what they say not what your futile ugly evil personality would like them to say
"That'll be the initial ratios Ophidian as per the logarithmic scale?
But the total exposure?
The Area Under the Curve?"
I thought you said you could read ? it's at 24 hours not time zero you utter utter plank read the slides and try just for once to actually interpret what they say not what your futile ugly evil personality would like them to say
Please show me where I said this is going to go over £2 you lying little .......
I said the data would be epic - and it will be.
You all love to scream Pump n Dump - what you actually mean is we're so confused what's happening - pathetic - just follow the pit pony's lead clipperty clop
To see a world in a grain of sand,
And a heaven in a wild flower,
Hold infinity in the palm of your hand,
And eternity in an hour.
.
.
.
.The bat that flits at close of eve
Has left the brain that won't believe.
The owl that calls upon the night
Speaks the unbeliever's fright.
.
.
.The gnat that sings his summer's song
Poison gets from slander's tongue.
The poison of the snake and newt
Is the sweat of envy's foot.
.
.
In the words of Lex Luthor "some people can read War and Peace and come away thinking it's a simple adventure story. Others can read the ingredients on a chewing gum wrapper and unlock the secrets of the universe".
Ignore lagattheback Bella - too old, too dumb and too twisted. Remember what I asked last week - who for and WHY ?