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Elimination: Doxorubicin: 1-3 hours; Metabolites: 3-3.5 hours. Terminal: 17-48 hours.
The fact there was a large amount of dox in the tumour (proven via biopsies) 24 hours after dosing is superb. Little wonder we have seen signs of efficacy already. Dox is usually given (if pos) for 6 cycles 3 weeks apart so 4.5 months whereas some patients have received 6000 for 12+ months as their disease has stabilised or indeed regressed so extended PFS and without the debilitating side effects. The platform is working as designed and now the trial has backed up the animal models (preclinical) I suspect the pipeline work will really whet the appetite of big pharma. An exciting H2 for definite.
No, it is 2 doses with a 2 week observsation period at the end, so 4 weeks per cohort. Period. That is the safety aspect for the SDMC to assess and approve esclation to the next dose level.
Tumour assessment (imaging, measuring) is carried out every 12 weeks (i.e. 6 cycles) for as long as there is no disease progression. This is for the efficacy aspect.
Facts are we have case studies in the 3w cohort that completely shut down Touk’s nonsense.
If the nephrologist is able to arm 3 cohorts to the warhead it will cleave the proton to the metallic surface of which pharmaceutical kokinetics can produce sperm into the tumour
This would enable the inhibitors to target plasma in the fap which would ensure doxorubicin could demonstrate far greater creativity in the membrane
Potentially giving us a share price of around £12.80
But remember I just done this by using predictive text which really annoys me
Onwards granny’s pants
Like I say, you're a twat:
Timster
Posts: 19,183
Price: 53.75
No Opinion
RE: 100x more Dox in Tumor vs PlasmaToday 14:03
Maybe Thorn is Dr Tapp he doesn't feel he can tell the rest of the world renowned experts on the SAB what he thinks so he puts his true thoughts on the lse board.
Much like Hurstbot hiding in plain sight.
Yep I'm just out on the chai run now.
I've filtered the morons ages ago, but as everyone else repeats what they say.
Touk, if you’re stating these are FACTS, can you please provide supporting evidence? Or is this your opinion?
Fact: AVA6000 half life is to low and it is being excreted too quickly
“Fact: a strong enough level of AVA6000 isn’t in the TME long enough to allow cleaving of efficacious level of dox to the tumour
Fact: p1 has been altered to more frequent dosing in order to try to counteract this issue
Fact; a new drug has been developed that doubles AVA6000 half life to try to counteract this issue
Fact: There will be a limit to the amount and frequency of AVA6000 that can be delivered if kidney damage is to be avoided.“
Especially the threat of renal dysfunction. No way on God’s Green Earth would Q3W move to Q2W if there was a risk of known, worsening, nephrotoxicity.
Actually that last comment of yours pretty strongly suggests you are just another sweatshop traffic generating troll.
Toukankahmoon, rather than asking the board to prove your negatives, why not reveal the sources of these “ facts”
**** off timmy boy, you have been replying to them all day, or too thick to realise?
FFS please just filter the 3 amigos we all know they talk utter garbage
Actually back over to you Touk to provide some references to back up your nonsense.
Touk where did you get all these facts from ?
See slide 17 …
https://avacta.com/wp-content/uploads/2024/06/Targeting-the-tumor-microenvironment-June-2024.pdf
Q2W 4 cohorts, 12-week cumulative dose (each), i.e. 6 doses. (10 weeks from 1st to 5th dose being given).
160mg/m2 x 6 = 960 cumulative –done.
200mg/m2 x 6 = 1200 cumulative –done
250mg/m2 x 6 = 1500 cumulative –underway (as of last week’s RNS)
310mg/m2 x 6 = 1860 cumulative –outstanding
Progress so far must mean overlap, so ch4 could start in next 2-3 weeks.
(Ph 1b = 3 x Expansion cohorts shown in the AGM pack).
Patient response to higher / faster dosing? How many patients still ‘on drug’ (Inc. Q3W)? Etc.
GLA
4 maximum 5 wasn't it.
I thought the second arm was only 3 cohorts in total?
“ You need a crystal ball CTSFO.”
We all do!!
GLA
Maybe Thorn is Dr Tapp he doesn't feel he can tell the rest of the world renowned experts on the SAB what he thinks so he puts his true thoughts on the lse board.
Much like Hurstbot hiding in plain sight.
Oh dear - seems Eggy is sulking now - not a good look eh? LoL
Don't worry Tim. 'It works'. That's why the share price is where it is after 3 years of the AVA6000 trial.
Just like you said it would be.
Glad I listened to you.
Did anyone who was at the AGM query as to why eggy wasn't on the SAB?
These useless feckers have no idea!
Notifications for dosing of 2nd and 3rd cohorts was just a month apart. All going well, we can expect notification for the 4th cohort at the end of this month, perhaps followed by some kind of initial read out in August. Exciting times!
You need a crystal ball CTSFO.
If the 2w data is very good then funding problems probably disappear there and then?
If they've misjudged it and the results are a bit ho-hum because the dosing interval is still too long then it might drag on a bit.
I'm assuming you can only move onto the dose expansion phase or Phase 2 trials using a dosing regime that's already been tested?
If they want to get these 'bang on' then might they still decide to further 'tweak' the 1a with a 1w arm or similar?
Do it once, do it right?
Thanks for your thoughts.
Thorn, thanks, just looked at the slide.
Looking at plain doxorubicin, there are mixed results comparing bolus dosing with continuous infusions. Sarcoma and ALL in children did worse with continuous infusions. So it isn’t as straightforward as it seems re dose and effect.
AVA6000 is both a new drug and proof of concept of a novel delivery system. Choosing doxorubicin is inspired because so much is already known about this warhead.
The t1/2 of AVA6000 is an interesting point. The fact that it is so safe means its peak equivalence concentration of free doxorubicin can be much much higher than plain doxorubicin at present. Q2W dosing again is showing a significantly improved safety profile. Does the move from Q3W to Q2W mean Q3W didn’t work? I don’t know. I’m more inclined to believe Q2W is the sweet spot of delivery interval, effect, and side effect. This mix making it much better than Q3W. And ICE has an important (very important) point. AVA6000 can be given more than 6 times. Tumour suppression vs outright complete destruction. People die with a cancer, not of a cancer.
The other platforms and t1/2 modulation I take to be of use with newer, much more toxic, warheads. Agree these will take much more money and time. But. Once Q2W is completed, assuming excellent results, BP will take Avacta more seriously and the IP they hold. I can’t see Avacta going it alone with its newer agents.
I guess they have to keep generating traffic for LSE by stirring controversy. They have become a parody of a troll though in their desperation to keep an angle open in the face of the inevitable.