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You’re absolutely right. My mistake, sorry. I read the paragraph in isolation, then the RNS. D’Oh. The infographic is far more useful.

MISTAKE IN TURNER POPE?

Looking at this in the RNS at time of the raise:

“ Significant Newsflow

The Company is anticipating the progression of its clinical development and research stage programmes to important value inflection points across 2024 and 2025, which includes key deliverables for the pre|CISIONTM pipeline:

· AVA6000:

o Read out of two-weekly and three-weekly dose escalation study data in late Q2 2024;

o Presentation of Phase 1 three-weekly study clinical data at AACR 2024 in April 2024; and

o Establish recommended Phase 2 dose in Q3 2024, initiating the dose expansion phase in the US in H2 2024, followed by the Phase 2 study, subject to funding and FDA approval.

· AVA3996:

o Complete IND enabling studies and submit IND/CTA application in Q4 2024/Q1 2025; and

o Initiate Phase 1a dose escalation study in the first half of 2025.

· pre|CISION? pre-clinical pipeline:

o Next clinical candidate to be selected Q1 2025;

o Tumour microenvironment activated drug conjugate clinical candidate to selected in the second half of 2025; and

o Further expand pipeline;”

I think Turner Pope have mixed up the dates of the Timelines. I think we’ll be getting important news in H2 2024. I can’t find any mention of H2 2025 and AVA6000 in Avacta’s RNSs. Sorry if I’ve missed it.

https://www.lse.co.uk/rns/proposed-fundraise-to-progress-therapeutics-pa5q71zfw9lgspt.html

FAPI-PET IMAGING IN SARCOMAS.

A very relevant paper.

https://www.sciencedirect.com/science/article/abs/pii/S0001299824000011

Cancer Associated Fibroblasts: their science and importance in cancer and potential therapies.

https://www.nature.com/articles/s12276-023-01013-0.pdf

Nikola Tesla died a penniless man when he should have been the richest man in the world. Science and commercialisation must go hand in hand, each part driven by people who are expert in their field. Imo businesspeople employ scientists, it’s not always good done the other way around.

In saying this, the science obviously has to come first. Getting to our present place has taken a lot of time and a lot of money. It’s biotech pharmaceutical research, it is what it is.

We’re on the cusp of very important news. The timeline isn’t that which was originally suggested, but it’s worth remembering the trials aren’t directly run by Avacta. They’re being performed on Avacta’s behalf. Not really fair to simply blame Avacta for the delays - though as said comms could have been better.

Results of Q2W may be the dataset that stimulates greater understanding and interest from BP. We know FAPI PET data is being added. That’s obviously brought more expense to the trial, and therefore has to bring significant value. I wonder if getting this arranged added to the delays? In which case it is Avacta that caused it, and an explanation would have been reasonable? To me Q2W now has much more importance than it did. Looking at Wyndrum’s comments, I think (hope) Q2W will be an SP reset event.

But this is AIM, let’s hope good news is allowed to raise and stay raised.

Good luck everyone, hope you’re having a great bank holiday weekend.

Excellent post. 🙏👌

He’s obviously well connected, he called the placing and sp drop right. But dig a little deeper into his financial services background and lots of questions need answers. That’s KPMG’s opinion. See the links in posts below.

TW has taken delight in insulting us as a group and certain members of this bb in person. Quoted their comments on his blog. A parchment thin skinned narcissist. He loves insulting everyone else, yet won’t correct mistakes / deliberately misleading (lies) on his own posts. Very sensitive about his dentition - childhood drug exposure - not cigs and an allergy to toothpaste. He isn’t a failed pizza boy cos he sold out at a profit!

Publishes out of Delaware US, conveniently protected from litigation re what he says.

Personally I pity him. Did p155 poor in PPE at Oxford, failed as fund manager, failed in the simplest fast food there is.

Those that can do, those that can’t become fourth rate share tipsters.

Good Afternoon NickE. I didn’t know this : “ It could be one of about five majors but my best bet is still Edwards Lifesciences . That's mainly because Rua non-exec, John Ely, previously led a research and development team there. There again, all the majors would be aware of Elast-Eon. Acquiring Rua for say £50m to £60m (which fits with the research note valuation) by either company would just be petty cash.” Edwards would make a very sensible first partner to trial the product. It’s going to get very interesting. I wish everyone the best of luck.

Those posts dealt with AVA6000 / Doxorubicin as monotherapy. That is hardly ever the case now. AVA6000 will make the trialling of different chemotherapy combinations much much safer. This might equally be the ‘paradigm shift’ in care we want to see.

Piecing this together. Not FUD or deramping or ramping. Plain Dox doesn’t work that well against STS for lots of reasons. There’s a potential for some of reasons to still impact on the effectiveness of AVA6000. But, and I think this is important. The lack of cardio toxicity means significantly higher equivalent doses of free doxorubicin can be delivered into the TME by AVA6000. Providing the drug moves out of the capillary and is cleaved by FAP quickly (almost instantly) there will be a spike of free doxorubicin within the TME.

This concentration gradient will drive free doxorubicin into the cells of the TME. This is also known to occur quickly, hence the rapid t1/2 decline of plasma [dox] following a bonus. Ideally, so much doxorubicin is being cleaved by FAP, the transmembrane transfer of dox from TME into the cell is the rate limiting step. This means the conc of free drug in the TME rises, concentration gradients with the tumour are minimised, and all cells uptake a therapeutic amount.

The relatively rapid Q2W repeat of drug will, again hopefully, allow the death of cells receiving the highest amount. These get removed, and the next closest get a high dose - ideally before drug resistance develops.

There is also a possibility of the intra tumour dox level being so high, different cell death pathways are triggered.

We wait and see.

Nearly there: this paper looks at drug resistance and the concentration gradient of the chemotherapeutic within the whole of the cancer. Not all cells are receiving enough drug to be killed, but enough to develop resistance. Similar to bacteria and antibiotics.

https://academic.oup.com/jnci/article/99/19/1441/2544230

This paper specifically looks at chemo resistance and hypoxia. More than just HIF-1…

https://biomed.papers.upol.cz/pdfs/bio/2015/02/01.pdf

In normal tissues there is regulated development of the blood supply to match the requirements of the tissues that are supplied. It’s all very different in tumour development. Though the growing tumour can stimulate angiogenesis (development of new blood vessels), these new vessels lack the planned development and functional maturity of normal blood vessels. There can also be a greater distance between the capillary and tumour cell / functional differences within the TME. This leads to groups of cancer cells developing in an hypoxic (low oxygen) environment. This changes their behaviour, including response to chemotherapy and radiotherapy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358492/

Either Touk or Thorn raised an interesting point about comparing the delivery of normal doxorubicin with AVA6000 and cellular uptake. It was a fair point, not FUD, and it gets very complicated.

Situation normal, perfusion of normal (non cancerous) cells and tissues. Every living cell in the body is dependent on adequate perfusion, adequate blood supply, to deliver oxygen and metabolites such as glucose, and to take away by products of cellular metabolism such as carbon dioxide. Typically every normal cell within the body is within 100 micrometers of a capillary.

https://training.seer.cancer.gov/anatomy/cardiovascular/blood/classification.html

Anyone interested in an update on STS oncology, doxorubicin, and the the problems to date in chemotherapy for this tumour? And why it’s so much more than a paradigm shift if AVA6000 works?

Afternoon NickE. Edwards would be a good fit tbh. But if it’s Medtronic, there might be a broader interest being shown. Medtronic took over Covidien in the past. They got the implant material Permacol as part of this deal. It’s an amazing product. The I wonder if Medtronic might want to broaden their implant material product range? Excuse the blatant ramping!

https://www.medtronic.com/covidien/en-gb/products/hernia-repair/permacol-surgical-implant.html

Sarcoma specific imaging with radio marker PET/CT.

https://www.sciencedirect.com/science/article/abs/pii/S0001299824000011

Afternoon Bella! Though tongue-in-cheek, you’re absolutely spot on. Theranostics - combining therapy and diagnostics within the same radio pharmaceutical - is an important, developing, part of personalised oncology. I think the Avacta platforms have huge potential here.

https://www.thno.org/

Reading the very helpful posts, I think this RNS is more important than I first did.

Knowing that AS always wanted FAP - PET scanning is huge, thanks for correcting me. Let’s assume this was always the plan, but potential problems meant it didn’t get mentioned early on - as suggested by B.V. This makes sense. Let’s also assume the data suggested Q2W was the better option early on. Combine the assumptions, then tell the world about it when early data suggests it’s going to be good news? BP gets a heads up that decent information, beyond the trial they expected, is on its way.

DYOR BTFSBITL

Timster - couldn’t agree more. This RNS should stop the daily downward sp trend, hopefully give it a boost - if AIM can start being a market and not a casino.

I’m wondering why FAP PET now? Not FUD, has someone had a quiet word? This may add clinching data for prospective partners / TO suitors.

GLA everyone.