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Thornogson=Eggy=Paid troll - see NFT's post today @ 11:11
Thorn, once dox is absorbed into tissue, what is the half life?
Thorn I hope you're getting paid per post. You said earlier, dox will be dox. Dox is cleared from the body in 24-48 hours. We had huge amounts in the TME after 24 hours so as you said dox will behave like dox. We are getting more dox into the tumour and it remained there after 24 hours so bodes well.
Doxorubicin, also known as Adriamycin or Rubex, is a chemotherapy medication used to treat various cancers, including leukemia, lymphoma, Wilms’ tumor, neuroblastoma, sarcoma, breast, gastric, bladder, lung, and thyroid cancer1. It works by interrupting DNA copying in cancer cells, leading to their death and slowing or stopping tumor growth. When administered intravenously, doxorubicin may cause a feeling of burning and pain. The medication is cleared from your body within 1-2 days after each dose, and you may notice orange or reddish urine during that time2. If you experience any symptoms like shortness of breath, chest pain, or irregular heartbeats, seek medical attention promptly. Additionally, certain foods and medications can affect its blood levels and effectiveness, so be cautious and inform your healthcare provider about all medications and supplements you take1. Remember to follow your care team’s guidance and report any concerning side effects.
A sufficient concentration to be effective......
for a sufficient length of time to be effective too Gje?
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Thornogson=Eggy=Paid troll - see NFT's post today @ 11:11
It doesn't matter how much is excreted as long as the dox is absorbed into the tumour at sufficient concentrations to be effective.
Blood pumping AVA6000
Yes it's not a passive process but an active one with blood pumping blood through tissues.
Some will meet FAP along its travels but most won't and for the AVA6000 that does there's a whole load of variables just there at the FAP interface, how quickly does it happen? How soon is the FAP free to cleave the next AVA6000 molcule?
This will all be important to Avacta trying to calculate what dose and frequency will maximise the Dox deposition in FAP +ve tumours to achieve the best possible results.
Fluid volume A and B!
Touk, you are just exposing your limited ability to think this through. Read it again. I'll repeat. In order to get the concentration of ava6000 at the tumour site to your desired concentration c, you'll have to raise the levels of ava6000 around the entire body to c. This can be maintained for some time at this level by reaching a steady state of ava6000 in and ava6000 out. The majority of ava6000 will be excreted without it passing by the tumour. Any that does can be cleaved by the fap.
The important metric, and try to focus on this, is the amount of dox that is cleaved and ends up in the tumour itself.
FYI Many clinical FAP benefits : Avacta using this type of technology in ongoing trials .
https://jnm.snmjournals.org/content/65/supplement_2/241401
"Conclusions: FAPI PET/CT demonstrated heightened and extensive uptake in ILD compared to FDG, with the WL-SUVmean emerging as a potentially pivotal parameter for capturing metabolic information in ILD. Notably, the FAPI WL-SUVmean showed promise in PPF prediction. These findings underscore the potential utility of FAPI PET/CT as an imaging modality for diagnosing ILD.
Figure 1, male, 46 years old, with IIP for 1month, manifests FDG and FAPI imaging positive. (A, E, the MIP of FDG and FAPI imaging; B-C, axial FDG PET/CT, CT and the FAPI PET/CT; The SUVmax of the foci indicated by the yellow arrow are 4.2 and 8.3 in FDG and FAPI PET/CT)."
That’s you done in 👍
https://x.com/MylesMcNulty/status/1808061031421235643
Well now we know paid stooges in a vindictive attempt to spam any sticks MM follows by TW.
Wow the desperate levels TW goes to to try effect people.
The beauty of Avacta is TW has got this so so so SO wrong and those with any short on right now are going to feel the burn 🔥
😊
Disagree Touk.
You were using the SAB as a platform to support your argument, when they have said or done nothing.
Gje306
That is so much crap. You are talking as if it’s osmosis. It isn’t. FAP is cleaving the AVA6000. There isn’t AVA6000 in the tumour. You are talking rot as usual
B2HSL
Exactly my point
We know no MTD was found so not a large amount of dox was cleaved outside of the TME. Ideally we would have had biopsies taken say 6 hours after dosing which will have likely shown more dox in both the tumour and plasma. The fact the biopsies were taken 24 hours after is a real plus and shows the relatively short half life isn’t an issue. Of course it can be improved upon for other warheads and the patents suggest this is the case (pipeline update will be super). We have very large amounts of dox in the tumours 24 hours after dosing and one of our independent oncologist’s amazed at the amount. Exciting for sure. Thorn could try and spread FUD more easily if the biopsies were taken a few hours after dosing but we got 24 hours.
Touk, How long has the SAB been in existence? Since Wednesdays announcement.
What have they said:
Nothing.
What are they doing:
From Wednesdays RNS:
We are bringing together a group of experts from head and neck oncology, sarcoma oncology, as well as cardio oncology, to help us with both AVA6000 as well as our pipeline.
It was important to us to have both UK / Europe presence as well as US presence as these are the
geographies that we are taking AVA6000 and our pipeline forward.
+++
Touk
"Nothing I have posted runs counter to anything the SAB have said or are doing." - They are not saying or doing anything.
You have proved nothing then.
+++
What Avacta have done by creating a Scientific Advisory Board, is to create a KOL.
KOL - Key Opinion Leader group.
A group that contains eminent specialists will have a certain amount of influence, and will be useful to state their points of views at the likes of AACR etc. A group that says 'we support Avacta in points various points of product development', and may come in useful with interacting with the FDA and other approval bodies.
However, their main reason for existence is "to provide expert insight and guidance on the ongoing clinical development of AVA6000 and the pipeline, including the pre|CISION™ platform."
Yes it probably is beyond you.
In order to get volume B up to the concentrations of A, then you will need to saturate A to the same level as C. It is a necessary requirement to sacrifice the majority of the injected AVA6000 in order to raise the concentration levels in the entire system. This is also the case for straight doxorubicin, the majority of it will not be reaching the the tumour, but alas it is not inert, so that superfluous dox goes on to kill healthy cells.
Now, on half life. It is true that for both straight dox and ava6000, that the majority is flushed out of the system without reaching the tumour. So when you say:
"If too much is just flushed out then that's not great."
then no, you are missing the point here completely. It is a necessary part of the mechanism of action that the majority will be eventually be excreted.
I'm sure Avacta are working on ways to modulate the precision based medicines, of course they will, they're aiming at leveraging the precision platform with many different molecules, which will all have their own pharmacokinetics. A mechanism to module half life will be another tool in the box.
Trolls don't answer questions, they only post rollocks and questions. Most popular thread ever, it's still going... 200+ replies, majority to garbled idiocy. As it turns out the subject of the thread is the most important. They shared pk data from the 3w trial, that tells how much is in the blood over time and we've been told 100x more in the TME for mid and high FAP, all whilst reducing side effects. It works.
Eggy: 'I think it might be beyond me truth be told,...' - Well if that isn't the understatement of the decade!! Whahahahaha
Disagree Bein, gje ran the numbers, even at this level it's nothing much. It's only short term if they're already working on offloading Dx. If they don't manage to divest it soon and it's cash generative, they can look to pay the CLN in Dx cash anyway. It's possibly only the next few payments that are up for debate really. I'd prefer them to keep cash, if they're confident of funds due to profitability/divestment/(deals!), they'll go for it.
Thorn are you still getting paid by Winnniifrith? If so that makes sense the dedication you have. Deary me.
I'd need to know the Plasma half life and the time of interaction at the FAP interface?
What's the FAP concentration and how long does the AVA6000 molecule take to fully interact with the FAP molecule to be cleaved and how long then until the FAP molecule is available again to cleave the next AVA6000 molecule?
I think it might be beyond me truth be told, but if Avacta are working on half-life extension molecules I think it's safe to assume that they feel the half life of Pre|Cision as it stands could be improved?
Please try and answer the question thorn.