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Does this make me winner of the FPD day competition?

Never mind. If dosing/treatment was a week ago then the patient hasn't suffered any severe adverse events. Just one question LDA: did you get your LLM from the same fixer ToucanOfDoom got his model?

Ah, £2.50 a share! The good old days of Covid, when we were all young and carefree and £2.50 really was £2.50.

As I wrote in the other thread, IMS Pharma Marketletter used to be a reliable source of information. Very sad to see this poor effort from what that respected publication has become.

"Founded in 1991, the newspaper was bought out of IMS Health by its editor, Barbara Obstoj-Cardwell. Originally known as the Pharma Marketletter, the paper has always had a broad distribution, serving readers in diverse markets around the world." https://www.thepharmaletter.com/about-us

An MCap of £5bn?

~$6.66bn?

For ALL of Avacta?

I should coco

Headquartered in London with research operations in Wetherby, UK

AVA6000 Advanced Solid Tumors (FAP+) Phase I None (internal) Phase I dose escalation ongoing; initial data expected H2 2025

AVA3996 Hematological Malignancies Preclinical None (internal) IND-enabling studies; clinical entry targeted 2026

Affimer Platform Diagnostics / Reagents Commercial Multiple partners Revenue-generating; expanding partner base globally

Latest Avacta Therapeutics News... 19 January 2024

IMS Pharma Marketletter used to be a reliable source of information. That ThePharmaLetter article is a weird mixing bowl of up-to-date and out-of-date information.

Well Timster...

ALS-6000-101 - A Study Evaluating the Safety, Pharmacokinetics and Early Efficacy of AVA6000 in Solid Tumours

...so it is like AVA6000, and every other first in human study because if they don't show some efficacy then they won't be continued.

Well stop acting like you're here to be right then.🤷🏻‍♂️

Well there's other stuff going on at the moment that's affecting the stock market such as the end of the tax year and the orange monster's adventure in the Gulf of Trump.

2/2

The two inventive steps that CC has outlined are 1) retention in the TME and 2) slow release. I believe that the Avacta chemists have played an absolute blinder here and I'm not surprised at the praise CC heaps on them. A big up for British education!!! The key is a chemical entity (a chemical structure) B that binds either very strongly or irreversibly (that's to say physically attaching) to a region of FAP that is a fixed distance D from the FAP cleavage site.

AVA6103 is thus a molecule with the following components:

B---L---pre|CISION dipeptide---SIL---warhead where SIL is the self-immolative linker.

It is this binding to FAP that holds AVA6103 attached to FAP for a long time (the retention in the TME).

L is a spacer of length gt D, the distance between the binding site and the cleavage site. And this is where it gets really elegant. True lateral thinking. The spacer L has all degrees of movement; it is like a link chain where the individual links have near total independent freedom of movement. If you throw a chain in the air and measure the distance between the two ends it will be anything from 0 to the length of the chain with the probability being weighted towards a short distance. And this probability allows the chemists to design a length of spacer to suit the drug's PK (remember CC's comment about being able to design the PK any way the potential partner wanted?) - so if you want a very slow release rate, the spacer is made just a bit longer than D so that the dipeptide is rarely within range to be cleaved (the chain rarely lands full length), and if you want a faster release (probability of a faster rate of cleavage), the linker is made much longer (greater chance of the two ends of the chain being fairly close together). It's all on probabilities amongst vast numbers of instances.

I've also looked at the self-immolative linker in that second patent. I see how the example I saw works and how it could be used for simultaneous release of dual warheads. In fact I can see how three and possibly even up to five warheads could be released at the same time, the only constraint being the 3D geometry of having so many groups (warheads) attached - it could get rather crowded!

Well, anyway, those are my understandings of what's in the patent in light of what CC has said.

1/2

I've been looking in some detail at the two patents that were published back in January:

WO2026002988 - Fibroblast Activation Protein Alpha Binder Proteins - https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2026002988

and

WO2026002995 - Target-Specific FAP-Activated Topoisomerase Inhibitor Conjugates And Uses Thereof - https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2026002995

The former forms the basis for AVA7100, the AffDC that uses affimers to bind to FAP (claiming these specifically but also covering other polypeptides/proteins), but it is the latter one which I think is of more immediate interest as it pertains to AVA6103 where the binding entity coverage is broadened to include small chemical entities that keep AVA6103 a 'small molecule'.

I think I've now worked out what AVA6103 is in general terms. I can't see any definitive chemical structure that is specifically claimed and, as the actual molecule hadn't been decided when the patent application was filed, I would expect a subsequent patent application to have been made that exemplifies and claims the precise molecule being taken into the clinic - that's the strongest IP protection one can obtain.

The 144 is for the whole of the Phase 1 study, the 1a dose escalation (2 arms, the Q3W and Q2W regimens) and the 1b dose expansion (1 arm) parts.

https://clinicaltrials.gov/study/NCT07454642?tab=study

"The first patient was dosed on March 31, 2026."

No, the first patient was dosed in the US yesterday, 30 March, or earlier if they wanted to wait a while in order to make sure there were no immediate adverse events from the first patient, first dose before reporting FPD.

This is the US 'press release': Avacta announces first patient treated in Phase 1 FOCUS-01 trial of FAP-Exd (AVA6103) - a sustained-release pre|CISION® exatecan peptide drug conjugate

https://www.globenewswire.com/news-release/2026/03/31/3265176/0/en/Avacta-announces-first-patient-treated-in-Phase-1-FOCUS-01-trial-of-FAP-Exd-AVA6103-a-sustained-release-pre-CISION-exatecan-peptide-drug-conjugate.html

It's the same as the RNS.

I wouldn't read anything at this stage into the use of "treated" rather than "dosed". Probably just the American way.

Whooooooshhhh!!!!!!

Exatecan found in urine and plasma plus patient not suffering terrible side effects or dead = working.

Wtf happened to April?

So called because he'll gladly take you for a ride.

It's difficult to reconcile this personality we're seeing with the calm self-assurance one expects of a former RAF pilot, 1968-72.

'That conference' being AACR

That conference is for preclinical data and Avacta has already announced their presentations. Strange though that there's been no mention, even by REACH, of the ICR presentation of their work with AVA6000.

I think the AVA6000 data will be presented at ASCO at the end of May