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'"Clinical validation is everything" says Jane Doe of Biopharma Analytics' - says a placeholder name from a generic company type company name - made me chuckle.

It's simple. Avacta can't take AVA6000 through to regulatory approval for both STS and SGC (unless there is a big injection of cash).

SGC is the low hanging fruit of an indication that responds very well to AVA6000 and for which there is no current standard of care.

AVA6000 still works for STS, not just with much kinder side effects but also because patients can be treated, and their disease progression held in check, for far longer with AVA6000 than with straight doxorubicin.

There is also always the possibility of licensing AVA6000 out to another company to take it through to regulatory approval for STS.

Radiopharmaceuticals are the flavour of the year. No self-respecting pharma company wants to miss out on the latest fad and risk being left behind by the pack.

And the Annual Report still says "The Company is informed that, at 5 June 2025, there were two individual registered shareholdings, Lombard Odier Investment Managers (holding 3.1%), and Conifer Management LLC (holding 3.1%) with more than 3% of the Company’s issued share capital."😉

That was 63.65% of issued share capital right there, and that's only those stockbrokers with retail investor holdings totalling more than 3% of the company's shares.

As far as I can make out, these are the last RNS's that notified TR1's. The titles of these RNS's have, for over a decade, been 'Holding(s) in Company'.

09 Jun 2021: Conifer, from 3.54% to 2.99%, 7,575,786 of ? shares

11 Aug 2020: Premier Miton, from 8.13% to 4.66%, 11,609,794 of 249,155,721 shares

Prior to that there was a whole flurry of TR1s in the spring of 2020 (Covid era)

It is noticeable that the TR1's are completed in a haphazard, inconsistent way, hence the '?' above for the missing data.

(^Bachovchin)

Our Gen 3 pre|CISION® pipeline leverages the highly specific binder proteins, the Affimer® proteins to create an entirely novel class of drug, the Affimer-DC (AffDC) which have 3 key advantages over traditional ADC. These antibody mimetics have applicability as biologics to oncology therapeutics and are currently being used in the development of pre|CISION® drug conjugates, that both significantly extend half-life and deliver the drug warhead intratumorally in a sustained release mechanism. Our first Gen Three candidate is a FAP-binding Affimer® drug conjugate (AffDC) designed to enable this platform to treat patients with cancers considered FAP low and extend the reach of the pre|CISION® platform.

I think this neatly summarises the holy grail of targetted drug delivery that Avacta have taken from Bacovchin's lab and run with. from the 'Key information' page ( https://avacta.com/investors/key-information/ ):

Avacta’s proprietary pre|CISION® platform masks toxic warheads by binding them to a short, engineered peptide that is cleavable only by the tumor-specific protease, fibroblast activation protein (FAP). The peptide is designed to disable the warhead before the cleavage step releases it directly in the tumor microenvironment.

Our innovative pipeline consists of pre|CISION® peptide drug conjugates (PDC) or Affimer® drug conjugates (AffDC) that leverage the tumor-specific release mechanism. The tumor-specificity of the warhead release and bystander effect optimization of our medicines provide unique benefits over traditional antibody drug conjugates.

Our lead pre|CISION® program AVA6000, a Gen One peptide drug conjugate form of doxorubicin, recently completed Phase 1a studies and is currently moving into indication-specific expansion cohorts in three diseases. AVA6000 has shown a dramatic improvement in safety and tolerability compared with conventional doxorubicin and multiple ongoing and durable RECIST responses have been observed in patients with FAPhigh and doxorubicin sensitive diseases. A significant concentration of released doxorubicin is observed in all patients with post-treatment biopsies, even in patients whose tumors have lower levels of FAP activity. In addition, multiple responses have occurred in patients with expression of FAP only noted in stromal cells (cancer-associated fibroblasts, or CAFs). This indicates that tumor cell expression of FAP is not required for the release of doxorubicin, with even lower levels of stroma-only expression being sufficient.

In the AVA6000 Phase 1 trial, we have observed multiple favorable changes in the pharmacokinetic profile of released doxorubicin, including a dramatic reduction in the maximal concentrations of released doxorubicin, reduction in exposure (AUC) and reduction in volume of distribution, essentially recapitulating the preclinical findings. The changes in the kinetics in patients underscore the mechanism of action of the pre|CISION® platform provide a framework for platform improvements in the PK of additional warheads.

The pre|CISION® chemistry has been optimized in our Gen Two PDC in the pipeline, whereby the conjugations are optimized to (1) significantly extend half-life of the conjugated drug and thus the released warhead and (2) modulate the rate of cleavage (kcat/Km). Both of these developments are anticipated to significantly alter the pharmacokinetic profile of a released warhead and enables our scientists to tune the delivery of warheads directly to the tumor with minimal peripheral exposure in normal tissues. Our first Gen Two pre|CISION® medicine is AVA6103, a PDC containing the most potent topoisomerase 1 inhibitor in clinical testing,

Cholseyn, you forgot to edit those last few lines of Tom's memo.

Never thought I'd agree with sheppy, but here I am, sat in my 911, cheering him on!

Switching accounts or two computers?

D-G wrote: "You don't seem to be a very fair minded contributor CJ.( I – for one – welcome Wyn's opinion.) "

That's because you're Winnie the Pooh's fluffer.

The babbling trader returns!

What I want to know is why hasn't Musk gone to Mars yet? He's talked about it for long enough and often enough, so why the delay?

See? That's analogous to the "Why hasn't XYZ happened with Avacta yet?" questions. More patients required.

Cj, just take a minute or two to sit down and consider the implications of what you're suggesting as that would apply for any company, any SAB, any drug, and no oversight. The SDMC, by whatever name it goes under (DMC, DSMB), is part of the process, along with the Ethics Committee, also known as an Independent Ethics Committee (IEC) or Research Ethics Committee (REC), which plays a crucial role in drug trials by reviewing and approving all aspects of a clinical trial protocol before it begins.

In a word cj, no. The SAB is too close to Avacta and therefore not independent. It would instead be the same arrangement as we had for Phase 1a with the Safety Data Monitoring Committee (SDMC), which still exists in some form to monitor and oversee the Phase 1b trial.

This is what Wiki says: https://en.wikipedia.org/wiki/Data_monitoring_committee

specifically https://en.wikipedia.org/wiki/Data_monitoring_committee#Overwhelming_benefit

Yes, you are.

Where is the AGM agenda? Was there an RNS about it? - I didn't notice one.

From the Corporate Governance page: "Darlene’s time commitment is one to two days per month."

And at £96,000 for six months in 2024 that's a nice little earner.

It's certainly not clear what value Darlene D-H adds.