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I was intrigued by Trapist®

https://www.youtube.com/watch?v=06KsqhGeaKM&ab_channel=CorisBioConcept

Investors getting in late ahead of tomorrow's RNS.

Yes, yes, intravenously, but the trick Kong is that it is administered by the light of a silvery moon. It wouldn't work otherwise. Very astute chap is Kong. Very much on the ball. Always knows the right questions to ask.

If you're that impatient roger then sell up now and put your money in the Post Office.

What a pity RAH no longer comes on here to defend his fantasy futures.😂😂😂

We had the best lone arranger.

🤡

great post jt, well argued. there are a couple of points though that i think could do with further discussion.

the data presented at science day was very sp**** and didn't show a clear dose/response trend. the margin for error is consequently very large. however i don't see how you got to ~16ng/ml for c6.

here are my workings for various scenarios, all assuming a linear dose/response:

taking the 4.9ng/ml of c1 (80mg/m²) as the base,

c6 (310mg/m²) = 4.9x(310/80) = 18.99ng/ml

taking the highest concentration, being 15.9ng/ml of c4 (200mg/m²),

c6 (310mg/m²) = 15.9x(310/200) = 24.65ng/ml

and for a c7 at the maximum allowed dosage,

c7 (400mg/m²) = 15.9x(400/200) = 31.90ng/ml

the last one is above the ~25ng/ml for the 50mg/m² dose, but the equivalent for 75mg/m² of doxorubicin would be ~37.5ng/ml, so in conclusion...

all calculations (being done on a linear dose/response) show free doxorubicin from ava6000 at 24 hours to be well below the normal level of naked doxorubicin doses at 24 hours based on calculations using the science day data and the report of ~25ng/ml doxorubicin in plasma from a 50mg/m² dose.

the second part of your argument, concerning the prevalence of side effects, is also well made. it is indeed a complex issue and we lack the important auc findings. i believe the difference between naked doxorubicin and the way doxorubicin is cleaved off ava6000 is important. the former is available in the plasma immediately, the latter only when ava6000 has found and been cleaved by fap. we don't know how much of the doxorubicin in the plasma never saw a tme (cleaved by fap outside a tme) and how much has leaked out from a tme. the single time point means that we also don't know the shape of the auc for doxorubicin from ava6000, nor how it differs from the shape of the auc for naked doxorubicin. the clinicians might know these already but the reliable and objective data we do have to go on are the reduced incidences and grades of doxorubicin side effects, so that's all good as well since, if the occurence of side effects is related to the auc, this means that the doxorubicin is very largely, massively even, being used up in the tme and... leads to progression free survival and potentially also tumour regression.

How weird that all uppercase got converted to lowercase...

great post jt, well argued. there are a couple of points though that i think could do with further discussion.

the plasma data presented at science day was very sp**** and didn't show a clear dose/response trend. the margin for error is consequently very large. however i don't see how you got to ~16ng/ml for c6.

here are my workings for various scenarios, all assuming a linear dose/response:

taking the 4.9ng/ml of c1 (80mg/m²) as the base,

c6 (310mg/m²) = 4.9x(310/80) = 18.99ng/ml

taking the highest concentration, being the 15.9ng/ml in c4 (200mg/m²),

c6 (310mg/m²) = 15.9x(310/200) = 24.65ng/ml

and for a c7 at the maximum allowed dosage,

c7 (400mg/m²) = 15.9x(400/200) = 31.90ng/ml

the last one is above the ~25ng/ml for the 50mg/m² naked doxorubicin dose, but the equivalent for 75mg/m² of naked doxorubicin would be ~37.5ng/ml, so in conclusion...

all calculations (being done on a linear dose/response) show free doxorubicin from ava6000 at 24 hours to be well below the normal level of naked doxorubicin doses at 24 hours based on calculations using the science day data and the report of ~25ng/ml doxorubicin in plasma from a 50mg/m² naked doxorubicin dose.

the second part of your argument, concerning the prevalence of side effects, is also well made. it is indeed a complex issue and we lack the important auc findings. i believe the difference between naked doxorubicin and the way doxorubicin is cleaved off ava6000 is important. the former is available in the plasma immediately, the latter only when ava6000 has found and been cleaved by fap. we don't know how much of the doxorubicin in the plasma never saw a tme (cleaved by fap outside a tme) and how much has leaked out from a tme. the single time point means that we also don't know the shape of the auc for doxorubicin from ava6000, nor how it differs from the shape of the auc for naked doxorubicin.

the clinicians might know these already but the reliable and objective data we do have to go on are the reduced incidences and grades of doxorubicin side effects, so that's all good as well since, if the occurence of side effects is indeed related to the auc, this means that the doxorubicin is very largely, massively even, being used up and working in the tme and... leads to progression free survival and potentially also tumour regression.

Just for information/interest:

https://www.globaldata.com/media/business-fundamentals/top-20-global-biopharmaceutical-companies-report-2-3-market-cap-growth-in-q2-2023-reveals-globaldata/

...when you see someone speaking about something you don't fully understand, remember this...

https://www.youtube.com/watch?v=KHbzSif78qQ

Do you know the mechanism of doxorubicin resistance Matml74?

Asking for a friend

I must point out that I separate my investment in Avacta from any emotional involvement around cancer. There are many ways to die and my friends and family have succumbed to several of them. The only thing that is certain is that one of the ways will get us in the end. Hopefully Avacta will lessen the chance of a painful cancer death for many, but that's not of much benefit if the death comes eventually from, say, dementia - assuming there are relatives/friends to suffer mental anguish.😊

Two points...

If it's known what the effect of doxorubicin in the TME at many times the presently achievable level is on drug resistance, then we have an answer. But we don't. We will ALL have to wait for the trials and reviews of the longterm treatment of AVA6000's doxorubicin on tumours in order to answer that question.

Secondly, the current AVA6000 paradigm is to target MORE doxorubicn to the TME at HIGHER doses and for MORE cycles. We are in uncharted territory. Patience is required in order to see the extent of progression-free survival and any tumour regression that may be possible or doxorubicin resistence that might arise.

Finally, we've many of us been there. My own dad, and his father before him, passed away with a cancer that could potentially be treated with AVA6000. I have a keen interest in AVA6000's efficacy.

Avacta are you listening? There is a needy PI fretting the weekend away.

Rather than signing up with a payment system to the free trial I opted to quickly select all and copy...

Fired up by AOH1996, the article is about these 'breakthroughs':

1. The tumour annihilator (AOH1996🥱)

2. A drug to supercharge your immune system - immunotherapy/checkpoint inhibitors

3. Vaccines that can cure cancer – and prevent it coming back

4. Flash radiotherapy (short burst of intense radiotherapy)

5. Super-viruses that can infect cancers

Whilst strictly correct, this is the sort of thing that leads to false expectations as it gives the impression that these people might be cured by this super new drug: "[AOH1996] is now being trialled in people for whom standard treatments, such as chemotherapy, have not worked." This is a first-in-human Phase 1 safety and tolerability study of course.

https://classic.clinicaltrials.gov/ct2/show/NCT05227326

It'll be many years before it can be prescribed, if ever.

As for the other 'newest breakthroughs to celebrate', well, something old, something new...

Let me put my point another way.

If AS had been asked about ovarian cancer instead of breast cancer at the AGM, what do you think his answer would have been? And in that case, would ovarian cancer now be Avacta's 'focus'?

...or Ovarian Cancer trial...

Excuse me, but it was obvious from Science Day that breast and ovarian cancer would be next.

https://avacta.com/wp-content/uploads/2023/02/MASTER-DECK-Avacta-Science-Day-23.02.23_compressed-1.pdf (Slide 87)

But none of that is imminent. We are still in Phase 1a. A definition of 'focus' is needed..

Beware speculators.

Is this idea being pushed by the Twatterati?