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Also, as the parallel study will start after C7 has been going for 1 cycle, quite possibly 2 cycles, for patient 1 or more, C7 will inform the parallel study about the initial dose level.

Forgot to add: I don't think Alan would talk about dose escalation in the parallel study unless it were approved by the FDA and was consequently being both teasing but vague about what it actually involved.

Alan said from 'shortly' until 'mid 2024'. About 8 months. I got the distinct impression that they want to do 2-weekly dosing because bam-bam-bam it will really hit the tumour hard at the sort of level we're already at. He said, or inferred, that the parallel study was to inform about the selection of the RP2D - and 8 months is a long time to stick at one dose level and I don't see how doing that would either inform about RP2D or provide useful information without a doxorubicin comparator. So maybe they'll start at a slightly lower, known (or educationally guessed) tolerable dose for 2-weekly cycles, and increase in up to two DEs. What really struck me was how positive Alan was that we were still (at 2.79 times standard doxorubicin) a long way from MTD which is why I think they will dose escalate in the fortnightly study. I may be wrong of course and they will select one dose level and do dose expansion (Phase 1b) using that but I don't really see what prolonged AVA6000 dosing will tell them that they wouldn't find out in Phase 2 - failure in a Phase 1b or failure soon after in Phase 2. And neither of them likely!

Had a reread of the RNS and relistened to the Vox interview podcast (https://audioboom.com/posts/8370233-vox-markets-interview-with-avacta-ceo-alastair-smith). Here is a rundown of the topics Alan addressed in that podcast:

0:55 overview/background

2:50 efficacy, tumour shrinkage

5:02 efficacy in STS subtypes

5:48 logic behind C7 (3-weekly dosing) and fortnightly dosing - FDA approval process is "quite short, so we expect to begin that study shortly (in parallel with C7) and complete [it] around the middle of next year."

7:45 optimal dosing regimen for Phase 2 which will be designed as a registrational study for STS

8:20 Phase 1a data release (C6+)

9:12 validation of pre|CISION platform

10:33 other susceptible cancers

11:51 commercial interest

12:51 shortened development time

Key amongst this are, I think, the noting that different STS subtypes react differently to AVA6000 (5:02) and the length of the parallel fortnightly study.

Clearly the choice, or rather the range, of STS subtypes in that fortnightly dosing study will be critical in defining exactly how well the different STS cancers will respond. And that study looks like a dose escalation study with up to 3 dose escalations of 2 months each. It will be very interesting to see at what dosage they start. Fingers crossed for 400mg/m² (equivalent to 600mg/m² on a 3-weekly dosing cycle)

As to noob's question about why the market hasn't reacted, it is the nature of the AIM market: short-term, impatient, gambling, chasing the next big thing, looking for big quick returns. One can guarantee that 90% of the retail investors haven't a clue even what Avacta's tech is and another 9.9% don't understand what it is or the implications of how good it is and how it could change cancer therapy. You hear this with the bland statements about drugs failing in Phase 3. These retail investors become interested when there are definite timelines for progress and revenue and may well go away, hoping to buy back in to catch the uplift of that progress and revenue.

Institutional investors have checks and balances to guide (limit) their investments. It takes time for them to react and the ones in the UK are very risk averse.

I take issue with one point you make about the pre|CISION platform Rambo. Whilst the tech will definitely allow the toxin warhead to be cleaved off in the presence of FAP in the TME, I don't think it is fair to make the assumption that the prodrug will be inert until that time; all prodrugs will need to be tested (at low dose) to show that the prodrug isn't metabolism to become ineffective or activated prior to being cleaved, just as AVA6000 was with the first dose being 90% of the lower standard doxorubicin dose.

And to restate your point about previously unsuitable tumour types now potentially being treatable with AVA6000, those cancers were not suitable because, whilst it has antitumour activity, doxorubicin isn't used because of side effects and total amount that can be given and because there are better alternatives. Those cancers are epithelial cancers with high levels of FAP and that makes them candidates for treatment with AVA6000.

'AVA6000 Phase 1b for Esophageal Cancer' is just a salad of words taken from the trial protocol.

Or do you think the AVA6000 Phase 1b trial will be for oesophageal cancer? 🫤

That is such a useless site. The titles are always a meaningless word salad.

Well cancer isn't going away and it isn't going to change. AVA6000 works and works consistently in the thirty something patients it's been tried on, apparently according to what Alan had said and written. So safety, tolerability and efficacy seem to be sorted.

That just leaves the questions of: 1) Is there anything better coming along? - no, not within the timeline during which AVA6000 will make it to market; and 2) Will a pharma company ignore our IP and make and market AVA6000 themselves? - no, that's not the sort of thing that goes on in the pharma industry (where IP weaknesses are exploited and circumvented) and, anyway, Avacta's patent has been granted in the US so protection is very high.

Anyway, you shouldn't take the word of anyone on here. DYOR! - and never invest more than you can afford to lose, even with Avacta, as there may at any time be something out of the blue affecting the whole market (Russia going nuclear for instance).

It's coming back to me now (read the article perhaps a year ago). The problem is that liposomes aren't of uniform size and, whilst the concentration of the drug in solution is uniform, the bigger liposomes will contain more of that solution and the tech measures the size of the liposomes.

Alan's interest in the company's tech may be to use it as an enabler for industry and/or for Avacta to use it, possibly with some targeting and release (disruption of liposome at required site of action), as liposomes mask the drug from the enzymes and immune system entities in the body.

The problem with liposomes (certainly in chemotherapy) has been the lack of uniformity in how much of the drug each liposome has encapsulated. This company addresses that by characterising the liposomes so that their production can be adjusted so as to find a formulation method that produces uniformity.

I'd like to wait until the revenue being provided by Dx is known (should get a good an idea next week) - that is, how far can it extend the comapny's cash runway for AVA6000 trials - before dismissing it and saying flog it. So Myles doesn't speak for me.

Excellent news! Worth an RNS? Or wait until we win?

Fyi, Scrip has a long history and is, or certainly used to be, the prime service for pharma news. A highly respected news service.

https://en.wikipedia.org/wiki/Scrip_World_Pharmaceutical_News

Where/when did Alan say there had been some shrinkage in other, non-STS, patients? The RNS said "there are further indications of clinical activity in patients across other indications" but that doesn't necessarily mean tumour shrinkage.

There are many ways the pre|CISION cake can be cut - and sliced.

My way of thinking is that Avacta want to take AVA6000 through to regulatory approval in the US for STS. At that point the drug could be licensed to different pharma companies for exclusive rights to market it in the various territories (e.g. GSK in Europe, J&J in North America, Merck in the Far East, Roche in MENA, ...and so on) with Avacta getting initial payments and milestone (for approval by other regulatory authorities) payments and a % of the sales (possibly different %s in different territories).

Clinical development of AVA6000 for other indications will need a lot of trials as doxorubicin is not first line SoC, trials on it's own and in combination with many different other treatments (chemo and radiotherapy as well). A LOT of cash would be needed for these so licensing out by indication (breast, ovarian, lung, etc) with exclusive rights to develop and market globally would be the way to go there with Avacta getting initial and milestone pyments and a % of the sales (again differing but this time different %s for different indications).

Then licence deals for pharma companies to use pre|CISION technology inhouse with their own toxin, a deal similar to the POINT Biopharma one but worth much, much more.

In short, the old banger that has been Avacta is going to be some super-valuable, fast moving Bugatti in the future!

https://upload.wikimedia.org/wikipedia/commons/thumb/1/18/Bugatti_Chiron_1.jpg/420px-Bugatti_Chiron_1.jpg 😁

I'd be astounded if these changes to the trial design - the parallel fortnightly dosing and the brought forward "potentially pivotal" phase 2 study - are not with a nod from the FDA and being worked out with the close collaboration of the FDA.

Just so long as he doesn't repeatedly blurt out Tourettish "transformative"s

Ah, but as per previous years, will the SP go down when Alan starts speaking, 90p, no 80p, placing or no 20p placing?

"Stifel Europe failed to get away a £10 million placing at 90p, no 80p, in mid June as I exposed HERE but, as I pointed out earlier this week HERE"

Interesting that TW should be admitting to insider knowledge, or was he speculating, no lying, or is he just a knob?

Interestingly also, he blocked me on Xcreta when I posed the exact same choices to him there.

I read it as HCI wanting shares now, which they can sell and make a profit on, rather cash later when Avacta is awash with revenue from a licensing deal or few.

This early repyment will reduce the quarterly repayments and interest charge. Not by much, but it will reduce them.