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Mostly ignoring this place - all the research was done, all there was to do was to wait. The board was a mire of nonsense quibbling over nothing. Not good for the noggin.
Now that there is something happening, I thought it worth a revisit.
I probably should have added...
Did anyone hear in the presentation a claim/plan to be trialling pro-Dox in Dox-sensitive patients in 1b?
Given the trial design is two doses vs vanilla Dox, to my logic they MUST be dosing Dox-sensitives; otherwise why the hell would they be using Dox-insensitive patients as the control group and given them Dox - a very potent toxin?
Am I imagining things or was it outright said/written?
A ramp I know: but to my understanding of drug trials they are cutting so many corners and basically going straight into testing efficacy in phase 1! Which to me can only mean that regulators must have given them a nod. It is obvious to many here than surely all Abakta need to do is show that the pro-Dox and the pro- bit are safe (check?) and than Dox is being dumped in heroic quantities - after all it is known exactly what the Dox is going to do. Perhaps regulators agree and 1b is all needed to get it fast tracked.
Bella, all (I think) the patients dosed so far have been Dox insensitive - the cancers they have will not respond to Dox, hence why they have never been exposed to it and hence can be given pro-Dox. We aren't going to hear of any miracle cure stories.
I think many people here were hoping for data that shows it works. I guess those people forget that phase 1 trials try to find out whether it is safe. Yes, there may be hints on whether it works, but given the very small number of patients tested on so far, it is dodgy statistics to start making claims of efficacy.
Did the Jan RNS say "It is safe"? It clearly read to me that is what the first four DE stages suggest. Can they run a science day (afternoon?) and flesh out the fact that it is safe? I guess so. There is a lot of nuance over the search for an MTD and what it means to not find one, etc. Would any of that be material? I won't be in the room, but I would guess it is easily possible. Their lawyers/compliance officer would make sure of it, I bet.
Given my understanding of the drug trials process, it gives me more confidence in Avacta, esp. the senior staff: they are doing clinical trials and are at the stage of testing its safety, so are only making claims that they can prove - it is safe so far; biopsies have shown cleaved Dox only in the TME. The fact that they are not making early claims, based on small data sets, is the right correct to do and we should respect that decision.
Dox is well understood. The dose-response curve was plotted long ago, i.e. the effects of various concentrations of the drug in the tumour environment has been studied. As with all drugs (up to a point) the more you give the more effective it is. Clinicians would like to give a dose of the drug that would maximise the concentration of the drug at the tumour site and have maximum effect, but in the case of Dox they cannot because of the severe systemic effects.
We are told that "the release of doxorubicin to the tumour tissue at therapeutic levels". What I'm waiting to hear is: at what concentration is the cleaved Dox in the tumour environment compared to the levels pure Dox establishes in the tumour environment?
The phrase "therapeutic levels" is explicitly used as a comparison to "the levels being detected in the bloodstream" but we hope is also as a comparison to the levels found at the tumour site when given standard Dox.
This for me leads to three (or vanishingly possibly four) outcomes:
1. The levels of Dox cleaved from the 6K are a fraction, e.g. 50% of the concentration that pure DOX establishes at the tumour site - 50% would be effective, just not as effective as pure Dox. This isn't much of a worry as we should be able to increase the dose of 6K significantly as we are not seeing any toxicity.
2. The levels of Dox cleaved are similar to what pure Dox establishes. Since it isn't showing toxicity, we might as well go a bit higher and see what happens.
3. The dose of 6K we're already pushing in can, in theory, release more Dox than a standard dose of pure Dox. So, perhaps we're already seeing a higher conc. of Dox in the tumour environment than pure Dox. "Good God", the clinicians are saying, this stuff is performing better than the mice models! How high can we go? Will we ever see an MTD? Does pushing a higher, but still non-toxic, dose give hints at tumour shrinkage that we can then properly test in 1b?
All three options to me are various levels of brilliant.
There is a tiny chance that "therapeutic levels" could be stretched to a situation where cleaved Dox conc. at the tumour site is low e.g. 1% conc. of the levels pure Dox establishes. It would be one hell of a conversation to be pushing in 100x the dose of 6K as we are now. And to get there would be faaaar more dose escalations and would in no way fit with the plan to start dose expansion mid-year. Not going to happen methinks.
Also: hello again. Still here. I just couldn't be done with all the squabbling over the last year or so.
They're in my town next. I've applied to be on the show and may get a call from the producers. I need to have two Qs lined up to get picked to appear. Most Qs on the show are, so I need mine to be snappy.
1. Near the start of the pandemic, when tests were scarce, Boris Johnson told us British tests were a little way off. We recently, effectively run out of tests but this time British tests are available. These tests cannot be used since the applications to allow their usage has sat unprocessed since August. How is this, to quote Boris, moving Heaven and Earth to support the British Diagnostic industry?
2. Recent data show that the three main vaccines have been shown to be at most 10% effective after 20 weeks after second dosage and re-infections are common. The government want us to live with Covid. What will that mean? Three or four boosters a year, regular isolation periods and continued reintroductions of measures to try to keep the infection rate down.
If these peeps have got hold of the virus: https://www.msn.com/en-gb/health/medical/christmas-could-be-saved-new-variant-lifeline-as-test-can-detect-deadly-strain-in-minutes/ar-AARbNjp?ocid=entnewsntp
Does that mean Abakta can also get hold of it? And in which case, should we imminently be expecting news that AffiDx can detect it?