Member Info for RorkesDrift

From

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647653/#SD1

Note W Tap study with normal dox.

Disease control rate was 62% with normal dox. Not sure of time point. Lots of other data points but read across requires standard warnings.

The 50% with ava6000 includes all patients rather than those on higher doses. The newer study starts at higher doses which from an ethical perspective suggests they think they are at least equivilent to normal dox. Be diffucult to fully inform a patient that you will receive a treatment dose known to be less effective.

Highlighting the requirement for high FAP makes sense but thats true before study started. Suggests that tighter inclusion criteria will further improve results albeit reduce population. Might be time to invest in FAPI-PET.

Avacta have the systemic pK curve for normal dox and dox released into the circulation from ava6000.

Assume all dox from ava6000 comes via conversion in tumour and all thst dox arrives in systemic circulation

The amount of dox in ava6000 is only relevemt if you know the % converted and remember all of that is hitting the tumour rather than being diluted in circulation as for normal dox.

From what has been said it appears that a third of the normsl dose appears in curculation so you can give for 3x as long. The tumour gets hit with huge dose but the body is exposed to far less.

This isvwhy it doesnt help to equate ava6000 atvan equivilent mg for mg dose - if 100% was converted and arrived in circulation the side effect profile would be very similar because auc and carduac exposure would be the same. You would end up.lowering the dose not raising it. Remembervall converted ava6000 hits tumour presumably at massive concentration

How many cycles per patient?

We know dox efficacy is related to dose - well the dose hitting the tumour. There comes a point where no increase in efficacy whatever dose.

Normal dox limited by toxicity so you cannot give maximum efficacy dose. This does not hold ava6000 back.

However, the pK of ava6000 will be influenced by how fast it is converted and how fast it is eliminated by the body.

Added to this efficacy is also affected by the number of doses. Insult the tumour, it recovers, you hit it again. And again and again.

The move to 2w dosing fits with the search for the optimum dose. High insult, low toxicity, maximum times.

Just to follow up on that. It would be unethical to give a patient an unlicensed form of dox when a licensed form is available if there wasn't good evidence of benefit over and above normal dox. That includes all future patients.

Timster.

And it works delivering 3.5 times a normal dose of dox with no dose limiting toxicity

Not quite true. The administered dose might be 3.5 times but avacta have already stated that not 100% is converted. Makes sense cause if 100% was converted it would presumably result in elevated systemic levels and toxicity. Not sure why Avacta continue to state the administered dose - if it confuses Timster imagine effect on the pom pom girls.

Some patients are responding and being left on treatment - would be unethical to do this if it didnt work given that treatment is not without its own burden, costs and risks. QED it works (to some extent, in some patients).

AS and EF have recently awarded themselves a shed load of new options. Thus enables them to benefit from any SP rise whilst not having to risk their own money. The recent raise must have been a strong possibility when these options were announced - just wondering if the performance benchmark is from 50p?

I'll try and help. This tests, which is still only on the bench, tests whether someone has malaria. The avacta test is to determine whether the parasite is drug resistant.

Hope that helps.

Thanks for posting. Did well to find it.

JT makes good point about the dry nature of scientific presentations. It goes along side that nothing is proven without the evidence, the whole evidence and....

The change in language I think (and its only an opinion) is driven by the overhype by MM and the pom pom girls. Anything vaguely positive is immediately translated into a series of absolute facts and pump several times a day. Given the loss some retail investors will now be in the nomad has probably advised not to supply the pump and dump brigade with the ammunition. AS actually called them out last AGM when he took the p 1 55 out of them claiming a cure for cancer.

There are gaps in the data - you can make up stuff to fill the gap depending on whether you ramp or deramp but the gap means the SP will change. One way or the other. Someone claiming they know which way beyond doubt has other motivations than your personal wealth position. In some cases its the exact opposite.

NY what matters is how much is hitting the tumour compared to a dose of normal dox. One way of increasing that is to give more frequent doses. Avacta will know the conversion rate because they are measuring pK of the leaving group. They have chosen not to communicate this to the people who own the company. I suspect potential new owners have seen it.

NY they haven't given 2x the dose of dox. They give ava6000 a % of which is converted to dox. The MOA is that concentrations are very high at site of conversion. See last set of Q and A which confirms it is notb100% conversion.

Probably worried about appearing to be boosting. Think they are going to need a bigger venue for next AGM.

Just seen bloke over on twitter collecting votes for no confidence motion

That's not a bad strategy but you would normally implement it before you spent a shed load of hard to come by cash on two overpriced Dx companies and then fail to leverage your own in-house IP

AS to board last week

Big science presentation at major event in April

Let's accelerate a book build before anyone sees this paradigm shift.

Whilst you are at it I've had ago at Dx for about 20 years and my last effort was truly awful. One day someone might get tested with an affimer they paid for. Until then would you mind reseting my options package.

Where is Mr 7 make it 8 questions when we need him?

Great made up word. Looks like it wasn't true.

Don't worry - again not true

Improve communications. I rest my case

EF do the honourable thing and just go. Hand back all your options and perks cause you haven't earned them. I really don't think we need to go through the whole appraisal, HR, performance appraisal thing do we.

Bump

Why would they buy shares when they award themselves massive option packages. They wouldn't risk their own money when they win massively if it comes off and lose nothing if it doesn't.

Who. How?