Member Info for Ronnycant

The science is doing well... that well, that some people/institutions/groups want some cheap piece of the pie, in order to help AS in his funding... We should have never been in this situation, but let's look forward.

I know I have extremely limited understanding on how cancer drugs work... The only thing that I can go by is the fact that:

EFFICACY:

cohort 4 they reach high levels of drug in the tumor of 1000 to 2400 nM (nanomolar) where the therapeutic levels generally reached by straight dox are around 400-500 nM. That is multiples in cohort 4 alone. There is a clear increase over cohorts, meaning, C5, C6 and C7 will add a few multiples of dox in tumor. Efficacy: Has to be a CHECK

SAFETY:

In terms of dox in blood peaks, straight after application of more then 80% reduction in Cmax over all dose levels compared to straight dox. 40-80% in total exposure over time... Safety: CHECK

MY MAIN CONCERN:

Delays due to slow patient recruitment. We're in the dark on that one.

In case they wait for 18th of March, then the news that will be dropped after is not expected to be good. Why wait with good news.

My next concern (and I am a holder, in pain), what is going on with the bi-weekly dosing study? Last thing I heard is that they are recruiting. Why have they not yet announced that they have dosed patients? Do they do this after a full cohort has been dosed?

So did they not manage to find sufficient first-line patients that fit the criteria? I think we have to get used to the fact that AS is drip-feeding the bad news. The next disappointment unfortunately, I believe is that the bi-weekly dosing study is running into several months of delay. I hope I am wrong. I'd be delighted to be wrong on this.

Chat GPT:

In oncology, a "therapeutically relevant dose" refers to the concentration or amount of a drug that is present in a tumor at a level that is sufficient to exert a therapeutic effect. This means that the drug has reached a concentration within the tumor tissue that is capable of effectively inhibiting or destroying cancer cells.

Achieving a therapeutically relevant dose within the tumor is crucial for the success of cancer treatment because it ensures that the drug can exert its intended anti-cancer effects. If the concentration of the drug in the tumor is too low, it may not be effective in killing cancer cells or inhibiting their growth, potentially leading to treatment failure or disease progression.

Therefore, when a drug is found in the tumor at a therapeutically relevant dose, it suggests that the treatment has the potential to be effective in targeting and combating the cancer cells within the tumor site. This information is important for assessing the efficacy of the drug and determining its suitability for cancer therapy.

The only item that is somehow still unclear is, is how much dox is being dropped of at the turmor. They indicated "therapeutically relevant"... how much is that? In the table they compare it with dox in the plasma after 24hrs... but there generally is hardly dox in plasma after 24hrs... That sounds like a low, almost irrelevant benchmark.

On the other hand, if if would drop insignificant levels at tumor-site, you would not stop disease progression in 3 end-of-treatment patients, nor reduce tumor volume in another end-of-treatment patient.

And indeed... efficacy is still unclear.. but signs of efficacy were generally not expected with these heavily pre-treated patients where the tumors have developed strong evasion-mechanisms. As a result, indeed, the responses that have been observed are a plus.

Assuming the bi-weekly dosing is done on first-line patients (C7, I'm not sure), that's where we are supposed to see true efficacy. Mind you, straight dox also only shows those in about 25% of patients. That's your benchmark. Fingers crossed.

Indeed... next year's AACR will be about 6k.

Forget my last post.

Who says I am against a BP partner? You'll get a quality deal when they realize you are not begging for cash.

"initiate"... might take a year before you have a buyer... by which time they will be cash generative.

They should now actively engage to sell DX. Buyers do not just come out of the woodwork when you need them. Get an extra 20 Mio GBP (or whatever they can fetch), to have a buffer... whatever it takes to get through phase 2 with AVA6000.

The CLN has a minimum conversion level you muppet, well above 50p.

Another muppet. It was oversubscribed. They elected to stick to existing shareholders

The CLN has a minimum conversion level you muppet

JRDC, I think you are on the ball. That is why now Christina Coughlin (American) is running the show, with Tap (American) his hospital (American). Let's do things properly, and let the American experts run the trial and deal with the FDA.

In parallel, start selling DX and further enhance cash runway to be armed against any further possible delays.

Bella, fully agree... In order to sell the platform as a whole, licensees might not want AVCT to take shortcuts but want to base their decision on a full trial set-up, including phase 1b. Ignore Icecool. He enjoys being deceived, sticking his head in the sand.

Whatever you say...

What is the Optimus project?

BTW, from the RNS:

The dose expansions are expected to begin in H2 2024 in the USA, followed by the Phase 2 efficacy study, subject to funding and FDA approval, which the Board considers to be a major value-driving event for the Group. The dose expansions are expected to be in several orphan indications including soft tissue sarcomas and the selection of these dose expansion indications will be informed by data from the ongoing two-weekly and three-weekly dose escalation studies.

Each to their own interpretation. I just hope they will sell DX by latest Q1-2025 to increase the cash buffer... even if they only fetch 15Mio GBP (massive loss)... buying time to progress AVA6000 inhouse for as long as possible is key.. Staying in the driver seat.