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Thanks for digging that form out Timster! Very reassuring. So much going on at Leeds. It does show just how much of a goldmine Avacta's Affimer platorm could become. I remember some while ago, I think it was Energyshares, remarking on what a shrewd deal Avacta originally did with Leeds - £1.5m I seem to remember for the Affimer IP rights.

Impressive indeed but I can't quite get my head around how or whether it all necessarily benefits Avacta? Avacta say that the IP for their Affimer platform is covered by several patent families. Does this mean anything Affimer that Leeds comes up with is, to put it crudely, expoitable by Avacta?

I did about 10 years bench chemistry - initially it can be interesting but after a while it gets horribly mind numbing.
Jeepers indeed!
Mr R, there is a saying about old chemists - they never die, they just fail to react ;-)

Thanks Mr A too, that's really helpful - I am/was a chemist too - a bucket chemist - I'm sure you know the sort - and long since retired - so your 'A' level refresher is well pitched!

Thanks re 5140 link gmcc - AVCT thows up too much science for my few remaining grey cells to take in - and retain! Hugely interesting though and wonderful to think how much future patients should benefit from it all.

Interesting MrA. For those of us, or at least me, who are not quite so familair with the biochemistry, could you please explain a bit more about 5140. And how much have Avacta said about it too. Thanks

In a way this harks back in a way to something FMcL said, that traditionally toxicity has limited the cumulative amount that can be tolerated by the patient but that now with toxicity no longer a problem higher doses are not necessarily where the benefit will be. It is something that intrigues me and which I posted about a couple of days back...

Transport and utilisation of AVA6000 toward and amongst the tumour cellular material might become a rate limiting step? In which case presumably an ongoing dosing regimen might be needed which ensures a supply of cleaved doxorubicin sufficient to match the availability of FAPa - degrading areas of the tumour according to where FAPa is present. There may be some sort of kinetic limit determined by the presence of FAP/nature/permeability of the tumour micro environment? I'm not expressing it too well perhaps!

But it might mean that AVA6k is best dosed differently to standard dox - to stretch the argument a bit - on an almost continual low level drip basis. Which I imagine would not be a problem absent any toxic side effects and given that doxorubicin will only be activated locally within the tumour.

Very good point Mr A

As pointed out by j_t 14.16 today, FMcL says that traditionally toxicity has limited the cumulative amount that can be tolerated by the patient but that now with toxicity no longer a problem higher doses are not necessarily where the benefit will be.

Perhaps having overcome the toxicity problem through the use of AVA6000, might an issue arise along the lines BlackCat was getting at? That transport of doxorubicin through the cellular membrane into the cell and the nucleus might become a rate limiting step? In which case presumably a dosing regime might be needed which ensures a supply of cleaved doxorubicin sufficient to degrade all the available sites - up to a certain limit determined by the nature/permeability of the tumour micro environment. I don't see this as a problem. But it might mean that AVA6k is best dosed - to stretch the argument a bit - on an almost continual low level drip basis. Which I imagine would not be a problem absent any toxic side effects and given that doxorubicin will only activate locally within the tumour. Just a thought?

Some very informative posts this weekend - and since the AGM generally - thanks RAH, jt, btl oakhurst et al.

Thanks for the interesting replies everyone - note to myself - patiently waiting for the trial results is the must do.

Wow, that was along one!

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?