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In patients with soft tissue sarcomas (n=17 evaluable), multiple tumor responses are observed, even at lower doses including one responder at the 160 mg/m2 Q3W dose level. The stabilization of disease despite the removal of the drug is observed in this indication as well, suggesting a highly-effective and durable treatment in this cancer indication. The key difference between the biology of many subsets of soft tissue sarcoma and other epithelial malignancies is that many sarcoma subsets demonstrate direct tumor cell expression of FAP, which could enhance efficacy. The vast majority of epithelial malignancies do not demonstrate expression of FAP on tumor cells, only on the cancer associated fibroblasts.

Cardiac safety data demonstrate that despite dosing of faridoxorubicin with a cumulative exposure up to 550 mg/m2 of conventional doxorubicin, no severe cardiac events were reported, either during the dosing timing or in the follow-up period. Echocardiogram (ECHO) data were analyzed similar to the liposomal doxorubicin label in the full cohort of patients and these data presented based on the cumulative dose received of released doxorubicin. These data reveal that only two patients demonstrated ECHO changes consistent with adverse findings, one patient treated below the maximum of 450mg/m2 and one patient treated to 500 mg/m2. This includes a patient reported previously experiencing the early dose limiting toxicity due to ECHO changes in the 120 mg/m2 Q3W cohort (grade 2 cardiac failure). None of the patients treated to the cumulative dose of 550 mg/m2 demonstrated observed ECHO changes. The cardiac safety data compare favorably to that reported with both the doxorubicin and liposomal doxorubicin respective drug labels.

Clinical pharmacology data with faridoxorubicin

Despite dosing up to approximately 4x the dose of conventional doxorubicin, the data demonstrate exposure of released doxorubicin in plasma and normal tissues is generally lower than that observed with conventional dose doxorubicin (75 mg/m2 Q3W) and the median tumor to plasma ratio is 100:1. The lack of toxicity is explained by the limited tissue distribution as well as limited first pass effect exposure of released doxorubicin (reported in Lahu et al. AACR 2025).

Biopsy and plasma data collected during the trial at 24 hours after the first dose demonstrate two key factors relevant to the pre|CISION® platform: (1) intratumoral concentration of the active payload is dose-dependent, indicating that the higher doses lead to higher absolute values of released doxorubicin in the tumor and (2) efficient cleavage of the PDC is observed in all tumors, even those with limited 1+ expression, suggesting the lower level of expression required for cleavage of the peptide is quite low, demonstrating the potential of pre|CISION® medicines in a number of other malignancies with lower expression of FAP.

Thorn unless the CEO is lying, AVA6000 extends dox's half-life so it is certainly not an issue. Jog on or stop peddling this half-life BS.

A bidding war would have happened before P1A data published for lead drug?

The point is the tricky bit is proven in human, preCISION cleavage and what it dumps in the TME is only proven in human re faridox but the point is that MoA is all important as without it it's redundant. Whether they dump dox, exatecan or 2 payloads doesn't really matter. The all important element is proven but of course once 6103 is in clinic and if it does what it's designed to do I can't see Avacta being independent long.

Mirriad needs an impressive Q4. Excluding revenues come the end of this month there will be £1.2m cash left so unless there is a serious uptick the begging bowl will come out early next year and if they need one again I can't see IIs supporting and Rembrand will say thanks for the clients and cheerio.

That said if they have a super end to the year the share price would multibag.

Https://x.com/rah00084/status/1991077055912349992?s=46

It does AVA6000 a disservice to say the linker in 2nd Gen Drug AVA6103 needs to be *proven*.

It is more accurate to say the *tweaking* of the (already proven) linker from AVA6000 needs to show it can enable sustained release (of Exatecan).

How?

By tweaking the constituents on the *already proven* linker.

Enhertu did it with their GGFG linker (inserted a self-immolative spacer)

Trodelvy did it with a short PEG to improve solubility of their payload (SN38).

Tweaking linkers is the nuts and bolts of ADCs.

Gen1 (AVA6000) > Gen2 (AVA6103) does not involve anything like the novelty the market assumes.

This engineering is what fine tunes current ADCs.

Listen to the clip.

If 6103 does what it’s designed to do and performs as it did pre-clinical I suspect the choice will be taken from us re when to sell as they’ll be an offer so a choice whether to vote yay or nay.

Hopefully 6103 starts by end of March, TNBC data let’s say May, initial 6103 Data soon after and surely it’s cheerio. Hope so.

Amazing therapies being developed and of course vaccines. Big pharma aware but still investing huge sums in ADCs etc as they’re aware that therapies will be needed in addition to vaccines.

The question is does a take over offer come soon after 6103 shown to do as if did preclinical and will that come before TNBC. A huge few months en route

I can't get a quote for 10k shares but I can sell 50k at 73.6p so any buy volume and we should be on the move and who knows 75p could quickly become support.

Balance sheet. SGC low hanging fruit so likely much quicker for approval and to market. Generate revenues there and focus on the beast. Makes sense to me given the limited resources.

So you admit your comment re PK more FUD?

Not the best Pharmacokinetics? But 6000 extended dox’s half-life by some 40% hence there was still loads of it in the tumour 24 hours after dosing. A quick search will tell you.

Thorn you’re like a broken record. You’re clearly not invested but insist on peddling the same nonsense.

SGC is small fry but without standard of care and poor PFS 6000 could capture that and some £250m revenue a year would be huge but yes 6103 could be a beast and has the potential to generate 10s of £bns. Once MoA proven in clinic I can see a TO so could be as early as next summer.

P1b SGC data before YE. TNBC in H1 and assuming 6103 dosing Q1 with speedy recruitment things could move quickly. The beast uses exatecan which has a shorter half life than dox so needed tweaking to ensure it doesn’t leave the body too quickly and improve its therapeutic index, enter gen 2 linker and capping group. Proving this in clinic will surely be the catalyst for major interest. Assuming it also translates in clinic Avacta won’t wanna license it and I suspect suitors will accelerate their courting.

If 6103 looks like it’ll perform as it has pre-clinical (early PK and biopsies will inform) it’ll certainly be a beast and a major won’t surely wait too long.

Avacta won’t get too far with combo but who cares as long as 6103 performs.

The scientific community seems to be coming round to the conclusion that PDCs will be the next game changer and an evolution on ADCs. preCISION overcomes so many of the shortcomings ADCs have.

https://x.com/blueberrymgmnt/status/1983277096807084335?s=46

Wyn, this is a beaut, even for you -

You are forecasting the future

Do you think some forecast the past?

Deary me still going on about half-life, your agenda clear as day so no point discussing with you.

Wow I forgot how impressive the biopsies were and remember taken at 24 hours. Can see the correlation between size of dose and dox in tumour (and plasma) and remember we are currently dosing nearly double the highest in the biopsies shown so cancer killing properties more than impressive.

Slide 84 -

https://avacta.com/wp-content/uploads/2023/02/MASTER-DECK-Avacta-Science-Day-23.02.23_compressed-1.pdf

Thorn the figures are laid out in a deck years back, think a science day when they laid out the figures for 6 biopsies

Thorn that’s nonsense. You need to look back. Massive difference with conventional dox which is why the therapeutic windows is so much better with 6000. 6000 clears less quickly (by 40% or so) with higher doses and much less systemic exposure. That’s been a constant.

i mean what was that? fluff? what was funny was saying they’ve hit profitability in the us for the first time. no ****. rembrand have all the costs and miri a revenue share they’d be an issue if it made a loss ffs.

no revenue guidance for h2 or fy. no material contract rnss so still delivering small campaigns of signage. they’ll need a super q4 or a raise will be worked on early next year.