Today, I shall be posting mainly as...29 Oct 2025 11:09
...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!
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