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DanGB wrote: "From Big Pharma’s perspective: Would we want to licence AVA6000 and advance it knowing that AVA6103 and its potentially enhanced derivatives could blow it out of the water?"

I previously sort of answered this but to be more specific:

If Avacta were to offer exclusive licences for use of AVA6000 in STS and SGC (either to a single licensee or a licence each to two licensees) then it could be written into the licence agreement(s) that no other pre|CISION drug would be licensed for STS/SGC without the AVA6000 licensee(s) being offered first refusal, and this term in the agreement to be effective for x years, say 10 or 15. That would allow other companies to license or partner for AVA6103, AVA6207, etc. but not be able to take them to market approval for STS or SGC.

From a patient point of view I'd like to see multiple deals with multiple farmers for multiple drugs covering multiple indications as that would be the quickest way to make the tech available to humanity. I think in that scenario Avacta would sit at the centre, arranging deals and taking income payments from the deals. All 20 of them, plus a few in the new Finance department.

The options and combinations are myriad - multiple pre|CISION drugs with one or more warheads, multiple indications, and multiple geographic territories.

And the options for deals can go beyond simple partnering and licensing out with exclusive or non-exclusive, time-limited or -unlimited variations.

If I were a big farmer I would be interested in AVA6000 for the indications I'm interested in (SGC, STS and/orTNBC) when the efficacy data is convincing enough to make an offer because a) as first mover I'd likely get decent terms in return for the kudos of my validation, b) partnerhip in particular would give me close working access to Avacta for the technical aspects, and c) such a deal would not preclude deals for other drugs and indications in the future, for which I'd already have a foot in the door.

Yesterday's webinar is now up: https://www.investormeetcompany.com/meetings/investor-presentation-951

The Avacta company profile has been updated. Gone are Diagnostics, old AVAs and Wetherby. In comes a generic description that will last a long time:

"Avacta is a clinical stage life sciences company developing an innovative proprietary drug delivery peptide drug conjugate (PDC) platform, pre|CISION®. The pre|CISION® platform uniquely enables the repurposing of a range of oncology drugs as PDC payloads with the goal to significantly reduce toxicity and side effects for patients by concentrating the drug directly in the tumor. About Avacta – www.avacta.com"

Eggy, do you really not know why doxorubicin was 'selected'?

None of this is new but it is to you as this is the first presentation you've attended/watched.

I was very disappointed. No mention of whom we are in discussions with or names of warheads, not even the slightest subtle hint, and no word about how many $bns, not even ballpark figures. I needed those because if deals are announced out of the blue the shock may kill me.

A few small wording changes, notably more prior lines of treatment allowed.

What's happening with AVA7100 is a question that I posted during the webinar so, as that question wasn't preselected for the webinar, it won't get answered when they produce the Q&A - unless CC takes on board my frustration about how poor the published IMC Q&As are, being just an unedited voice record of what was said during the webinar (Ferry Docks, etc).

Being taken over isn't the only, nor is it probably the quickest, way to get pre|CISION drugs into real patients.

What risks do you see B2H?

It was actually my question verbatim, and I refer you to my earlier response to you in the Investor presentation thread at 11:29 on 24 Oct 2025:

"But let's look at the relative merits of a single combo drug (A) vs a two-drug combo therapy (B).

"A will have a single PK profile, B will have two PK profiles with - here it comes... - two half-lives, etc.

"A will require a single regulatory authorisation, B will require three authorisations (although the one for AVA6103 should be assumed as given) and that means clinical trials for both drugs and then for the combination therapy (so two additional sets of clinical trials for B rather than one for A), which means a lot more time and expense to get to market for what might be marginal, if any, difference in efficacy either way.

"A will have a fixed ratio of the two component drugs (supposedly 1:1), B will indeed be flexible - which seems to be your argument - but how beneficial would that be if the two components are needed to work together and different ratios (but always with more FAP-EXd) could be achieved by mixing, or giving separately, AVA6207 + AVA6103?"

yes, roll on sixteen hundred hours. just be thankful i didn't impose some of the others on you, including...

ronnie barker explaining the poster with alliteration, and again in ****ney rhyming slang.

julian clary doing it with innuendo (yes b2h, i had tried that, but it was far too crude).

the carry on cast doing a scene from a carry on movie, and again with innuendo.

donald trump speaking to an eight year old (that one was actually very easy to follow - even the hemo crowd might understand it) and again to a five year old.

meanwhile, at the macdonald's in the westfield shopping centre, near to avacta's white city labs...

Well it's clear from that that you don't know how the grading of side effects works nor what constitutes a DLT.

@MrJinx, do you know the gradings of side effects and definition of a DLT?

Suddenly, the door bursts open with a thunderous BANG. In strides a ramrod-straight figure in full dress uniform, medals clinking like a cutlery drawer. His moustache is so stiff it could slice bread.

GENERAL (Graham Chapman):

ATTEN-SHUN!

Howerd! Carr! What in the name of Montgomery’s left boot is this infernal pantomime? I’ve seen more discipline in a herd of inebriated gazelles!

Peptides. Payloads. FAP cleavage. Good God, man, this isn’t the music hall, it’s a war room! Avacta’s not prancing about with handbags and confetti, they’re mounting a precision strike on the tumour!

(points at the poster with a swagger stick)

Look here, you blithering thespians: Pre|CISION® – a targeted delivery system. FAP-specific cleavage. Dual cytotoxic release. Exatecan binds topoisomerase I, MMAE disrupts microtubules, PARPi/ATRi block DNA repair. Result? Apoptosis. Not “ooh missus,” not “titter ye not” – total cellular annihilation.

(leans in, voice drops to a growl)

In vivo efficacy in FAP-positive spheroids. Synergistic index >4. Resistance overcome. Therapeutic window expanded. AVA6000 in clinic. AVA6103 Q1 2026. This isn’t Carry On Doctoring, this is Operation Overlord for oncology!

(turns sharply to Frankie)

And YOU, Howerd – stop mincing about with your “double-decker whoppers”! This is a first-in-class dual-payload peptide drug conjugate, not a sodding kebab van!

(to Alan)

And you, Carr – less Beyoncé, more Bletchley Park. These aren’t “fabulous little wonders,” they’re engineered warheads with British ingenuity!

(stands to full height)

Right. Poster’s sound. Science is solid. Avacta’s advancing the line. Now fall in, shut up, and let the boffins get on with winning the bloody war on cancer.

DISMISSED!

(marches out, door slams, medals still clinking)

Ooh, Alan, my dear, Alan Carr—titter ye not! You come sashaying in here with your “Avacta” malarkey, all peptides and pipettes, like some glittering lab-coat diva. Beyoncé of biotech? Missus! I’ve seen more glamour in a chemist’s window display of corn plasters!

Peptides, you say? Sounds like a posh word for “tiny little stitch-ups” to me. “Oh, they can find diseases, fight diseases, deliver drugs…” Cor! Next you’ll tell me they can pop round, do the ironing and still have time for a quick cha-cha-cha before tea! British flair? Darling, the only flair I’ve seen in a lab is when the Bunsen burner sets fire to the technician’s toupee—ooh, the drama!

Cancer, diagnostics, drug delivery—steady on! You make it sound like they’re running the NHS gift shop: “Two peptides for a pound, love, and a free lollipop if you’ve got the Big C!” Red carpet? Champagne? The only red carpet in science is when someone spills the haemoglobin sample—splat! Front row? They’re more back row of the church hall pantomime, shouting “It’s behind you!” at a malignant tumour.

Smart? Stylish? Saving the world? Please! The only thing they’re saving is the catering budget by nicking biscuits from the tea trolley. Avacta—tch! More like “A-vacant” when it comes to a decent cuppa and a biscuit that isn’t a Rich Tea!

Ooh, no, missus… don’t encourage me!

...Frankie Howerd

https://avacta.com/wp-content/uploads/2025/10/AACR-NCI-EORTC-2025-Avacta-Dual-Payload-Poster.pdf

Ooh, missus! Titter ye not, but listen—here’s a right carry-on down at Avacta, where they’ve only gone and invented a double-decker whopper of a cancer-killer! Pre|CISION®, they call it—sounds posh, don’t it?—but it’s basically a sneaky little peptide that toddles up to the tumour, all innocent-like, with two naughty payloads stuffed in its handbag.

Now, the star of the show is this FAP—Fibroblast Activation Protein, luv, keep up!—which is only found loitering round the tumour like a dodgy geezer outside the chip shop. FAP whips out its knife—snip!—and suddenly, tada!, out pop two killers: exatecan (the DNA-twister) and either MMAE (the microtubule mangler) or some DDR inhibitor (PARPi or ATRi, the DNA-repair blockers). One snip, two wallops—bosh!

They’ve got graphs, bless ’em—LC-MS, western blots, the lot. Compound A, Compound B, linker this, capping group that—ooh, it’s all very technical, but the gist? Without FAP, nowt happens. With FAP? The tumour gets a proper seeing-to: TOP1 levels plummet, γH2AX goes through the roof, cells arrest in S-phase or G2/M, and—kerpow!—apoptosis! Cleaved PARP everywhere, like confetti at a funeral.

And in them 3D spheroids—proper little tumour snowglobes—they only work when the FAP+ fibroblasts are in the mix. Add a FAP inhibitor? Pfft. Nothing. No kill. Like sending a vicar to a rugby match.

Synergy? Ooh, missus—FAP-Exd plus DDRi is four, five times deadlier than exatecan on its tod. Resistance? Pah! They’ve outsmarted it. And the best bit? All this mayhem in the tumour, not in Mrs. Jones next door. Less toxicity, longer treatment, happier patients.

Avacta’s got two in the clinic already—AVA6000 (doxorubicin’s posh cousin) and AVA6103 coming Q1 2026. First dual-payload peptide drug conjugates, not them fancy ADCs everyone’s banging on about.

So there you have it—titter ye not, but science has gone and got itself a double act. One peptide, two payloads, one FAP cleavage—naughty but nice!

Either that or AI in Gyles Brandreth mde.