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I didn’t take it as a dig, not for one second, but it’s a learning point for me. Always check and double check. You’re absolutely right dox isn’t going anywhere, and might be coming back.

You must wonder what the motives are behind some advisory notes that get issued.

PL75.. I’m guilty of not doing t enough research as well! It was the first thing I found. You’re right, the Lumis note is completely worthless.

Let me correct that:

If all continues as at present, AVA6000 will completely change the dosing schedules of doxorubicin. We can only guess how high the TME / intracellular levels of doxorubicin that will be achieved. This potentially changes everything.

Morning all. Got to add in here.

OH FFS, FFFFS.

Quick google search of new treatments for Soft Tissue Sarcoma came up with this:

“ Olaratumab is intended to be used in combination with the cytotoxic chemotherapeutic doxorubicin. This combination is approved for treating patients diagnosed with types of soft tissue sarcoma for which an anthracycline chemotherapeutic such as doxorubicin would be an appropriate initial treatment and whose cancer cannot be cured with either radiation or surgery.”

There may well be newer, focused, treatments available or becoming available. But chemotherapy is very much about combination therapy. As seen here.

The other blatantly fecking obvious thing the ‘expert’ at Lumis fails to understand / mention / should have worked harder in school: AVA6000 opens an entirely new avenue of research. The present max dose regimes of doxorubicin will - potentially - be done away with. Whether that’s plasma max concentration or total lifetime max dose. This may mean different cell death mechanisms get triggered within cancer cells. Buenavista can correct me here: we might see the intra-tumour cell doxorubicin level rise so high, it stops / reduces the risk of multi drug resistance developing.

Please don’t take this as being blinkered to the risk of new treatments becoming available. I just think Lumis are showing surprising ignorance of the potential of AVA6000 and the pre/CISION platform.

No RNS by 18:30 last night re extension of PUSU regs. I think this is a good sign. The trading update RNS was as up to date as it possibly could be. Gut feeling is we’re getting a definitive RNS tomorrow re the takeover. Might be worth a little flutter if not released at 07:00. I don’t think the people mounting the taking private bid are walking away. Good luck everyone.

Pharma3 👏👏👏👏👏🙏

Well said Sir!

I hope everyone has a great weekend, and doesn’t (hasn’t) get affected by the weather. Here’s looking forward to more and more good news.

The problem is the difference between what the market values it at today vs its potential value in the long term. The combination of geopolitics and RS missing deadlines and simple stupid mistakes like the CLN has put us where we are today. There have clearly been funding issues since the failure to raise $20,000,000 last and this year. The more recent fintech problems in the UK haven’t helped.

It could be argued that 1:1 share in new company OR £1.50 a share, when sp is between 65-80p is good value. Personally I agree, I think it’s worth more. But that’s a long term view, not how the company finds itself today.

None of this is ideal.

Put us on the roof. Emergency Blow.

C’mon fly big D!

Chopper, just so sorry you’ve had to go through this. Utterly …. Well there’s no adequate words.

The hunger and ‘roid rage’ are very hard side effects to have, or see in loved ones. Truly destroy quality of life, as you so clearly explained. It must have been horrible for you and family.

The potential for focussed effect : minimised side effect is huge with these platforms. The majority of us will have personal / family connections with severe illness. In my case my wife has had a kidney transplant. It is what it is. Seeing transplant immunotherapy is one of Avacta’s interests is very very encouraging. Fingers crossed they can deliver for us all.

Final comment, FAP and poorly livers.. looks like cFAP (circulatory FAP) can be used as an indicator of severity of fibrosis. It might be useful.

https://article.imrpress.com/journal/FBL/24/1/10.2741/4706/4706.pdf

Thank you. Another useful thought:

“ Concentration of FAP is one thing but what's important to pre|CISION is the 'Activity' of the enzyme because it has to be active to release doxorubicin. The presence of FAP alone does not mean there is activity.” AS.

This is a cut and paste from the notes made at the TG meeting with Avacta. Just because FAP is being expressed, doesn’t mean it will react with pre/CISION. The trials will tell us. I don’t know how active FAP is in liver fibrosis. I’m guessing Avacta have considered this.

This is from the Avacta 2022 comprehensive update to the market:

“ FAP is expressed on the surface of specialised fibroblastic cells which are abundant in the supporting stroma of most epithelial cancers.

FAP expression is difficult to detect in adult non-diseased tissues, but is greatly increased in sites of tissue remodelling, which include liver fibrosis, lung fibrosis, atherosclerosis, arthritis, tumours and embryonic tissues. FAP expression is seen on activated stromal fibroblasts of more than 90% of all human carcinomas. The pre|CISION™ substrate can be chemically attached to a chemotherapy to generate a selectively activated chemotherapy designed to limit cell penetration and biological activity until it is specifically released by the presence and enzymatic activity of FAP in the TME.”

The company is aware of where FAP is found. They are bound to have considered this in their development process.

Hepatotoxicity is front and foremost in the development of any new drug. It has to be, the liver is the main organ for metabolising and removing drugs from the body. Not the only one, but the main one.

Not unreasonable to mention FAP is found in a fibrosed liver, but Avacta are bound to have considered this. Where do you find FAP other than cancer cells? will have been part of the development process.

It’s also worth mentioning that hepatotoxic reactions are seen with a large number of drugs. Paracetamol, for example, can cause horrific liver damage following a relatively small overdose.

The trials will establish safety, and if any patients will need to be excluded. Or if any specific investigations be needed. Such as FibroScan / MREs. It will become part of the standard work up of the patient.

Also worth pointing out that a significant number of chemotherapy agents are hepatotoxic:

Another overview:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8332851/

Hepatotoxicity with doxorubicin is rare, but well recognised. It’s not unreasonable to draw attention to a potential risk of AVA6000 in patients with underlying liver fibrosis. More importantly, AVA6000 will potentially be much safer in patients with normal livers. So keep healthy and thin before your cancer.

A recent update on the hepatotoxic effect doxorubicin:

https://www.sciencedirect.com/science/article/abs/pii/S0024320520303477

“including case studies if that is permitted. “

This is potentially important. This is a P1a trial. Designed and powered to establish safety and MTD. I don’t think it’s normal - please correct me - to include formal case studies in the data released about these trials? We know the narrative out of the company has changed to being far more positive vs neutral about this drug. They clearly want to share good news, with evidence to back it up.

I hope this next bit doesn’t sound too stupid… we know the patients in the trial will have kept to protocol during the trial duration. Once this time period is over, could they have had further doses of AVA6000 out of trial? If they, and their Oncologists, have seen positive therapeutic effects that they didn’t expect, could they have continued to receive AVA6000? Could this be part of the case study that needs permission to be published?

Please don’t take this as blatant ramping. I think it’s very difficult to stop a drug if a significant positive response / result is being seen.

Rose tinted glasses here as well. Any scientific data should be accurate, robust, QCd, and open to scrutiny. To me, it sounds like they have true sit up and take notice data coming out. Not the typical Phase 1 ‘it didn’t kill or cause serious harm’ type of message. Fingers firmly crossed.

Timster… I doubt it!