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Timster posted;
“1. AVA6000 exhibited rapid distribution, with a half-life of 45 minutes backing up my assertion that dilution in the bloodstream is too rapid.
Comedy gold 😂😂😂😂😂”
Tim all you have shown here is that you haven’t bothered to read the article that started this thread off.
Watching
What is inaccurate about the fact I have quoted?
Winne has gone sheepy has gone now it’s. Touks shift
Ice
Yes of course I understand that and I wouldn’t be surprised if they move to a weekly dosing regime to keep the levels of AVA6000 as high as possible in order for as much as possible to be in bloodstream around TME. And of course it’s the precision of AVA6000 that enables this and why we are all here invested.
You do realise they can administer many cycles over the current treatment of Dox hence why we are seeing results in patients that are still on this chemo approximately a year at a lower dose of AVA6000. It’s the cumulative dose that’s important and number of cycles over the current standard toxic version of the chemo.
CTSFO
Yes if the rapid reduction in free AVA6000 is mainly due to it being cleaved in the TME then that is brilliant, but as I say based on the overall results including biopsies and what has happened to clinical trial design, then IMHO, it isn’t, it’s being excreted too quickly. Perhaps our metabolism and kidney function is far better in this respect than mice?
Dilution in terms of parts per million of AVA6000 versus blood. As uncleaved AVA6000 is excreted (or whatever the correct term is) from the body, the amount in the blood decreases. That’s what I mean by dilution. Therefore less available in TME to be cleaved.
Lovable
You are quoting dox half life. That is meaningless in my argument (other than ensuring that any cleaved dox that escapes from the TME is excreted quickly before it can do much harm to other organs). I was referring to the AVA6000 half life stated in the original article.
Touk, it’s not a dilution that’s taking place. That would mean the the mass of drug has remained the same and blood volume has increased.
So the Pt1/2 of AVA6000 is going to be caused by its breakdown at the TME (good), breakdown throughout at non cancer sites (bad), and clearance of AVA6000 by kidneys or liver (good as long as no toxicity). All drugs have to be removed from the body - one way or another. So if the t1/2 is mainly because of FAP breakdown of AVA6000 at the TME, this is actually a good thing.
Also biopsies are of course are taken by different people and even with normal doc will have variables with the same dose as we are all different. An important take away is you can see a correlation between dose and dox. Higher dose higher dox. Yep it works as it should.
Touk, given the following thresholds for the various mechanisms of action of dox:
DNA adduct formation 25nM
Free radical formation/cardiomyocyte apoptosis1 100nM
Topoisomerase Inhibition1 400nM
And that DNA adduct formation is the mechanism of action that provides the greatest effect in reducing the tumour size, and that the range discovered in tumours was 76-2310, it suggests there is sufficient dox getting into the tumour, and all but 2 of the biopsies exceeded all the threshold above.
Now it would be good to have a chart which demonstrated the efficacy of dox (at least in average terms) against values from these thresholds and above. This would really put the argument to bed. I have had a scour around but cannot actually find any relevant data - as AS himself stated was the case a while back.
1. AVA6000 exhibited rapid distribution, with a half-life of 45 minutes backing up my assertion that dilution in the bloodstream is too rapid.
Comedy gold 😂😂😂😂😂
Doxorubicin, a frontline drug used in cancer treatment, has been employed for over 30 years. While it can cure certain cases, it also poses toxicity risks to major organs, particularly life-threatening cardiotoxicity. This toxicity necessitates dose-limiting treatment1.
Here are some key points about doxorubicin distribution:
Initial Distribution Half-Life: Approximately 5 minutes, indicating rapid tissue uptake.
Terminal Half-Life: 20 to 48 hours, reflecting slow elimination from tissues.
Seriously will stick with the case studies and real life result’s, than pay attention to Touk the Sunday scientists analysis. Only takeaway he should be involved with is the pensioners fish and chips on a Friday.
For me this is the clearest analysis of trial results. An excellent article but my takeaways are:
1. AVA6000 exhibited rapid distribution, with a half-life of 45 minutes backing up my assertion that dilution in the bloodstream is too rapid.
2. Tumor biopsy data demonstrated a mean concentration of doxorubicin in the TME of 860 ng/gm (range 76-2310 ng/gm, n=9). Which leads me to believe that there needs to be a lot of work done on targeting patients and dosing regime.
3. In contrast, blood samples collected at the biopsy showed a circulating free doxorubicin concentration of 8.3 ng/ml (range 2.4-15.9), indicating a higher concentration of doxorubicin in the tumor relative to plasma. Obviously supporting the conclusion that the platform works.
So we await the results analysis of arm2 to find out whether I’m selling my house to upsize or downsize 🤣🤣🤣. That’s a joke BTW.
'Could those believing this is a peer reviewed article please explain their reasoning'
BV, to be fair, the 'key highlights' section was probably written by a sub-editor who has made the writer of the piece pretty angry too.
"The phase 1 trial aimed to investigate the efficacy and safety of AVA6000 in patients with FAP-positive solid tumors, focusing on targeted delivery and therapeutic outcomes."
So, not your normal tolerability and safety Phase 1 trial then. Stopped reading after that.
Could those believing this is a peer reviewed article please explain their reasoning, preferably by interpretive dance for my added amusement.
Https://avacta.wistia.com/medias/b74537ezmn
This presentation rather tucked away in the ‘ other resources’.
It’s the most telling summary delivered well.
Investors should review .
Sound.
The immediate priority is to commercialise the pre|CISIONTM platform.
For those that have the where·withal & foresight to see it through should eventually be a win/win for everyone involved .
The goals of the company need updating but some still valid (albeit execution so far somewhat open to question -fair enough )
---------------
"Our mission is to improve patients’ lives and grow shareholder value by developing novel cancer therapies and powerful diagnostics using our proprietary Affimer® and pre|CISION™ platforms. Clear communication of our corporate objectives and keeping our shareholders up to date with progress, as well as informing potential new investors about the investment opportunity, is at the core of our communications programme. I hope you find the information you are looking for and welcome any feedback
ALASTAIR SMITH, CHIEF EXECUTIVE OFFICER"
The immediate priority is to commercialise the pre|CISIONTM platform.
For those that have the where·withal & foresight to see it through should eventually be a win/win for everyone involved .
The goals of the company need updating but some still valid (albeit execution so far somewhat open to question -fair enough )
---------------
"Our mission is to improve patients’ lives and grow shareholder value by developing novel cancer therapies and powerful diagnostics using our proprietary Affimer® and pre|CISION™ platforms. Clear communication of our corporate objectives and keeping our shareholders up to date with progress, as well as informing potential new investors about the investment opportunity, is at the core of our communications programme. I hope you find the information you are looking for and welcome any feedback
ALASTAIR SMITH, CHIEF EXECUTIVE OFFICER"
AS always said that it was important that any trial results were peer reviewed... and there you have it in black and white a positive peer review.
Good find by https://twitter.com/Mstambo999 , great summary.
Importantly, published in the ‘Onc Weekly’ segment of ‘Physicians Weekly’ and headlining Prof Banerji, our AACR24 poster presenter and Deputy Director at The ICR and Royal Marsden.
“U. Banerji and the team aimed to assess the efficacy and safety of AVA6000 in FAP-positive solid tumors. Preliminary results indicated promising antitumor activity and support ongoing dose escalation studies to further evaluate its potential in clinical settings.”
Looks like progress to date now being ‘owned’ by top oncology clinicians.
GLA
I wonder who will be the first troll to take this from the top spot !
Brilliant article !
Good article
"KEY TAKEAWAYS
The phase 1 trial aimed to investigate the efficacy and safety of AVA6000 in patients with FAP-positive solid tumors, focusing on targeted delivery and therapeutic outcomes.
Researchers noticed significant antitumor activity in FAP-positive tumors due to high doxorubicin concentrations in the TME, which supports AVA6000 efficacy."