Charles Jillings, CEO of Utilico, energized by strong economic momentum across Latin America. Watch the video here.
Hi Bella - I hope going forwards Avacta will be able to demonstrate the effectiveness of AVA6000 as a Therapy by harnessing the Efficacy of doxorubicin but with a much higher therapeutic index such that the Safety limitations associated with doxorubicin - i.e. the lifetime limit no longer apply.
Options will then probably abound on defining new dosage and dosing frequency protocols for Cancer therapy.
Ophidian
Since some seem capable only of providing insults and vitriol rather than content – even when given the space and invitation to contribute, I will provide some information.
Drug Efficacy is defined as the capacity to have an effect (pharmacologically).
After Fifty years, the Efficacy of doxorubicin is well known, well documented and well understood.
For Clarity, we do not want AVA6000 to have any Efficacy as an important part of it’s design is that is in fact completely inert in the body and has absolutely no pharmacological effect whatsoever.
Alastair Smith pointed this out in his video explaining the data from the AACR Poster and it has been shown multiple times in different Avacta slideshows and talks.
This 1a trial is seeking primarily to demonstrate the Safety of AVA6000. An important part of that requirement comes from the fact that the 5140 leaving group (unlike doxorubicin) had never been in Humans before and so it was necessary to show both AVA6000 (uncleaved) and the 5140 group (post cleaving) had no capacity to cause adverse events in Human subjects.
Now as the doses are escalated if the AVA6000 as everyone hopes and expects is being cleaved in the TME by FAP then the concentration of 5140 will go up as will the concentrations of doxorubicin hence the escalations are testing the Safety of AVA6000 not the Efficacy.
Drug Effectiveness is defined as How well the drug works (usually defined as within the usual clinical settings). Whilst similar to Drug ‘Efficacy’ it is different in that a drug may have a high ‘Efficacy’ but because of it’s poor ‘Safety’ and the number of undesirable effects it causes it is not ‘Effective’
We want AVA6000 to be demonstrably ‘Safe’ and to be highly ‘Effective’ by being inert in the body in it’s delivered form. By being specific in that it is ONLY cleaved by FAP. We want that cleavage to occur (demonstrably via Biopsy and metabolite data) in the TME.
We will get an answer to ‘Safety’ from Phase 1a and a hint about Effectiveness but it is phase 1b and latterly in Phase 2 that AVA6000 will be proved Effective.
As an aside – the Efficacy of doxorubicin will be able to be further exploited by delivering it as AVA6000 rather than dosing it directly because it will likely be proven to be Safe in higher relative concentration in the TME than can otherwise be achieved (demonstrated by a lack of (we hope) or reduction in adverse side effects experienced by the patients on the trial)
Ophidian
ps
to be useful - definitions are best looked up in a drug development handbook, pharmaceutical development guideline or pharmacology text book rather than Websters or Collins dictionaries etc.
" 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
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
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
sadly AVA6000 has no efficacy whatsoever as it is by design inert. The 1a trial was (is) seeking to prove the Safety of AVA6000 because the 5140 leaving group had never been in a Human.
Ophidian
this 1a trial is proving safety. Doxorubicin has been proven to have efficacy but has a limitation on the safe use of the drug up to a lifetime limit.
As Donald Trump showed in his stupid comments - Bleach has efficacy in killing among other things COVID19 but it doesn't have Safety.
Just like Bleach won't become less efficacious when used in excess - neither will doxorubicin, it's Safety however is very much a question to be answered (and with two successful dose escalations so far that question is being answered very favourably I would argue).
Ophidian
Fair enough @Apre simply trying to help and avoid spreading the impression there is something new or important in that piece. One mans tautology is another mans reinforcement of a point I suppose. Good luck.
Ophidian
This is not new news ! - it comes from the poster delivered at AACR this year and explained in a great video by Alastair Smith. The cytotoxicity data are for AVA6000 assessed in cell lines compared against straight doxorubicin - nothing to do with efficacy just simple safety. Whilst it's great data it's now pretty old news and isn't really pertinent to the CT data we expect very soon.
Ophidian