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So where does all my supposition lead? Well without the need further dose escalation, reporting on Phase 1a middle of this year early Q3 must be easily doable. And since AVCT say the two US sites are not being independently run, in the light of UK experience presumably they would treat US patients at the 120mg/m2 second cohort level but not go beyond this.
Clearly my suggestion that a second dose escalation has been considered clinically unnecessary and hence unethical is pure speculation and I am sure I will be put right if I have it all wrong - not least when we eventually have news from AVCT.

I have a science/chemistry background but not in pharmacology or medicine and I’m pretty ancient! So treat my thoughts accordingly – though to be fair they’re based on my doing a good bit of digging around to better my understanding of P1 trials and AVA6000 itself.
First doxorubicin is a very powerful drug used to treat a wide variety of cancers and has been in use for a long while. Thus its efficacy, characteristics, dose optimisation, etc. are very well established. But unfortunately, there are the serious side effects - hair loss, nausea, vomiting, mouth sores, reduction in bone marrow efficacy and not least potential damage to heart cells, which mean it can't be taken indefinitely. All well known.
AVCT think they have a way to eliminate all these downsides, which is what they are currently trying to demonstrate in the ongoing trials.
Up to now we have heard just two things from them. That results have been ‘remarkably consistent’ and that the initial 80 mg/m2 dose has been raised to a second 120 mg/m2 level.
As to a possible further dose escalation, either this has not yet been disclosed or maybe there is another possibility - that it has not been considered necessary?
Firstly what does ‘remarkably consistent’ refer to? Presumably not to the efficacy of the drug at the two disclosed dosing levels, as these are close to established levels typically used by clinicians, albeit subject to severe side effects, as above.
As others here have suggested therefore, it could be that the performance of AVCT’s version of AVA6000 is ‘remarkably consistent’ in that - as hoped - severe side effects have been consistently absent. If they have been it seems likely that this can only be for one reason, which is that AVCT’s pre|CISION FAP-alpha prodrug release mechanism has worked as expected. As a biochemical mechanism it will have presumably worked consistently or not at all.
Might it also be reasonable to assume that if the biochemistry is consistent then correspondingly there may be some consistency between the pharmacokinetics and tumour regression amongst patients with similar cancer types.
Then there is the question as to where they are up to with dose escalation? From what I have read the guiding principle for dose escalation in such trials is to avoid unnecessary exposure of patients to sub optimal, excessive or unnecessary dosing – anything else would be unethical.
Could it be then, that with adverse side effects eliminated and with dosing being done at levels known to be effective, patients would derive no additional benefit if dosing were raised to a higher, second level? Has dosing another cohort at a second level of escalation been deemed inappropriate?
Also if Avacta’s prodrug mechanism is working, as others here have also suggested, higher concentrations of active AVA6000 may have been released in the immediate environment of the targeted tumours, which would also mitigate against another dose escalation?
Continued...

I'd like to go back to the interesting links that actually kicked off this thread please.

In the oncology YouTube Amy Turner, who is working for Darren Tomlinson at the Leeds Astbury Centre for Structural and Molecular Biology, says she is developing affimers to link with RAS protein in cancers, which she hopes will result in news ways to treat, for example, pancreatic cancer. In passing she says she would welcome industrial support/sponsorship - something of that sort.

Avacta’s website says the Affimer® platform is Avacta’s proprietary therapeutic platform with its intellectual property covered by several patent families.

Can some kind soul who understands these things better than I do explain whether or not, or how and to what extent, Avacta would or would not (!) have some sort of first refusal on new therapies of this sort?

Doing such a smaart deal, which I agree it really was, says to me AVCT is a pretty smart company! Interesting too that Prof Bachovchin founded Point?

Timelines are usually uncertain and often slip in this sort of work. I don't follow the commentary on Twitter and here closely but I gather some see 'mid-summer' as being critical? I am not sure how these two remarks made in the Investor Meet Q & A square with that?

"We will only be able to update the market on biopsies and other clinical data when the phase 1a study is completed and the data have been fully reviewed."

"As discussed in the presentation, Phase 1a data for the dose escalation is expected in Q3 2022."

Good morning and, as posted earlier, the golden rules here are:

1) Don't respond to or add to the drip feed of 'harmless opinion' - filter the sea lions.
2) Ignore any poster or topic that is discussing the share price or it's imminent movements.
3) Soak up all you can from posters sharing knowledge relating to the science (some of which are really brilliant) and from posters who research relevant information such as new appointments and the science taking place with partners/competitors.

This is how they used to do:
Jamnes Simpson, together with his assistants were in the habit of experimenting with chemicals in his dining room to see whether they had any anaesthetic effect. On the evening of 4 November 1847, they tried chloroform, a substance they had previously ignored as unpromising. The immediately effect was elation followed by a sudden loss of consciousness. On coming round the following morning, Simpson knew that he had found a substance that he could use as a general anaesthetic. He repeated the experiment on his niece with the same effect. He began to employ chloroform in childbirth on 8 November 1847 and described its uses in a pamphlet Account of a New Anaesthetic Agent. Within weeks of its appearance, chloroform had almost completely replaced ether as the standard anaesthetic.
Come on Avacta!

54retiresoon - The path to remaining independent is for Avacta to continue licensing deals with multiple big Pharma companies across the spectrum.

I agree, It is worth comparing AVCT with ARM - and their IPR licensing model - they remained independent for some 20+ years after listing and were eventually bought, for what, £7bn?

Oops meant to put this here - AS may already have had tentative approaches from companies seeking to license AVA6000 - subject to confirmation of the expected good P1 DE results mid-year?

Presumably AS may already have had tentative approaches from companies seeking to license AVA6000 - subject to confirmation of the expected good P1 DE results mid-year?

And its fair to say its so true!

Hi TTB, have AVCT said at any point how many DE steps they might make in P1A?

Thanks Mr A. From the pov of an individual patient in a trial that appeared to be giving me new hope, I would certainly want every opportunity to volunteer for a further 'escalation' of my treatment. And if the AVA6000 programme is going so well. it would seem perverse if Avacta's Safety Monitoring Committee and the MHRA or whoever failed to accelerate it - greatly expand the number of patients involved. etc. But then all this is totally outside of my field of knowlegdge!

Re what you say Wiggly about it not being ethical to carry on when no improvement is seen... is there ever the opposite case in trials like these when it becomes obvious that a treatment is extremely successful, to such an extent that it is unethical not to accelerate approval and use?

Well pleased with all of that.

Best wishes from me too Poirot - on my occasional forays here your posts are amongst the sadly too few standouts. Looking forward to your return

Thanks Stodgy, that was in the final, busiest week during my six months of upheaval - now thankfully all over! Its not surprising I missed it! Very interesting. And that the story is being picked up in the Telegraph today is interesting too.

Much as I would have liked to, for the last six months or so I've not had the time to keep up with all the sleuthing, the news unearthed here about Avacta - and the follow up discussion. I still hold shares though and in the last week or so have dipped in occasionally. In this thread these snippets have caught my eye:

"Medusa19 beat some major diagnostics companies to self test approval in Europe... " "We only just have HUA give it time for them to finalise contracts."

Could some kind soul point to where / when this was announced / unearthed. Has AVCT confirmed HUA approval in Europe.

I imagine there must have been extensive discusssion on here when all was revealed? Roughly when would this have been - so I can attempt a search back?

One of the statistics I read recently was that the average age of those currently being recorded as dying within 28 days of positive COVID test is 85 and that on average each had 5 comorbidities - other conditions and circumstances which make them vulnerable. These are people dying with Covid and not necessarily of it. I am in my late seventies and at my stage in life it does cross ones mind that one might pop ones clogs fairly soon! During one of the Downing Street press conferences in the first lockdown Van Tam made what I thought was a most ludicrous remark. He said we can't let our old people die. What are old people supposed to do for goodness sake.

Thanks doze - I've not been following posts on this board anywhere near as closely as I once did and missed this. FDH