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Why don't we all set out exactly what Git has contributed to this BB this year?

I'll start:

Warning: narcissistic bullying incoming😉...

Actually if you want to average it Prof Eggy, then it would be 60% *** lower than standard dox***, not 50%.

But probably not a good idea to average such an important parameter.

Welcome AimHunter. Looking forward to more of your informed posts.

(Hope that wasn't tooooooo narcissistically bullying for some of the woke snowflakes on here.😁)

Great find ES. This comprehensive document provides, inter alia, answers to all the FUDsters' clinical 'concerns'. They're not new answers, just laid out very clearly for all to read - the FDA, clinicians and pharma industry professionals are not stupidly fumbling around as the FUDsters would have you believe!

Yes, I feel also that 2024 will be the year. "There is a tide in the affairs of man that, if taken at the flood, leads on to fortune." Just be patient and wait for the tide to come in.

I will now cease my narcissistic bullying ...for today.

Yeah but HurstBot is like https://www.youtube.com/watch?v=7yNV-GXoeCM

@JT

I've never seen the 'Optional spacer' exemplified and frankly don't understand how it would work. Cleavage takes place at the amide bond between the -C(=O)- at the righthand end of the 'FAP-substrate' and the adjacent -NH-. When the resulting H2N- is on the 'Active agent' then that active agent is the pure cytotoxin.

That's all very straightforward. However if the adjacent -NH- is on the 'Optional spacer' then the active agent has the optional spacer tacked onto it. If the active agent were doxorubicin then what's been cleaved off is doxorubicin with the optional spacer blocking the amino group end. How we get from there to pure doxorubicin is what I can't fathom as it hasn't been exemplified. Maybe that part of the IP is just there to cover all bases. Maybe there is some extra mechanism envisioned that extends the half life and is cleaved off in some way.

The 'Capping group' is different for AVA6000 and AVA3996. Why this is so isn't explained. If the capping groups have been optimised for each active agent being carried, then how, within the scope of the IP, is the best capping group for a particular active agent decided? Computational chemistry and molecular modelling and trial and error I should imagine. That doesn't make the IP useless, just not as straightforward as 'plug and play'.

Try here: https://www.linkedin.com/in/simon-bennett-0390796/

"Countering their lies with the truth is a powerful tool. Ridicule is another. "

Not true. Both of those just cause the 'discussion' to continue, which is exactly what the bashers want...

To my mind, the only ways to counter their influence on these BBs are:

1) to just state "That's not true",

2) to just state "[So-and-so] is a troll/trader/basher [take your pick]. Best ignored", or

3) to repeatedly challenge the troll/trader/basher to justify their untrue assertions.

If you give them NOTHING to argue against they will not be able to continue knocking the company. There are plenty of good posters and threads here where truth is spoken and if new investors can't tell the difference between the good stuff and the bashers who are being ignored/challenged, then they need to do more research of their own.

But unfortunately there are a lot of immature/insecure/narcissistic posters on here who will continue to feel the need to engage with the bashers to 'prove' their point. However, as they contribute no information, interpretation or insight they can be filtered without loss.

@JT, it would make sense for interested pharma companies to make AVA6000, and then AVA3996 when that compound's structure was published, and test for themselves in animal models to verify/invalidate the reported Avacta data. However when it comes to making and testing their own cytotoxins as pre|CISION prodrugs... which leaving group should they use? The AVA6000 one? The AVA3996 one? Another one within the scope of the IP coverage? One that is outside the IP coverage (difficult since the R-D-Ala-L-Pro- sequence is the heart of the invention, and hence 'the invention', and only the R can be varied)? What are the 'rules' for selecting the leaving group to make the best (inert, cleavable) prodrug? I doubt they could get much guidance from Avacta since this is Bachovchin's tech and it was Bachovchin's group that decided on the structures of what we now call AVA6000 and AVA3996 as, at least, workable prodrugs to target the warheads to the TME.

I would love to know why the leaving groups of AVA6000 and AVA3996 are different. When I saw that they were I knew that AVA6000 didn't prove the pre|CISION platform, only that the pre|CISION platform was proven for AVA6000. Subsequently the platform is proven for AVA3996, probably... will need to be proven in humans. There is nothing new here. Pharma companies will be wondering the same... What will it take to optimise their most cytotoxic compounds? What structure for the leaving group? Not necessarily a big problem if you want to play suck it and see and the time and expence involved in that but pre|CISION is not looking to me like a 'plug and play' platform - could be a reason why we've never seen any serious follow-on reseach compounds using all those out of patent anticancer drugs. Happy to be proved wrong with multiple licensed prodrugs using the AVA6000 or AVA3996 leaving groups...

Hurrah!!!! Someone's found batteries for our dear little android.

Where have you been HurstBot? We were worried you were lost and maybe rusting somewhere.

Why do people waste their lives arguing with a sealion?🤷🏻‍♂️ Insanity!

The case for AVA6000 is very straightforward. Increased efficacy and reduced toxicity/side effects of the v very definition of targeted delivery and biopsies have shown that doxorubicin, an approved and much used cytotoxin, is present in the TME.

QED

All that remains is to identify the best dosing regimen for the most susceptible cancer types (i.e. continue Phase 1) and do the study (pivotal Phase 2).

This development time and the correspondingly reduced patent protection time for those drugs that make it all the way to market is the reason why branded drugs are so expensive. It's just the way it is.

Also written as H2N- it is called an amino group, as in amino acids, the acid part of which is the -CO2H group.

https://media.geeksforgeeks.org/wp-content/uploads/20220114130256/Aminoacid-300x183.jpg

Good point made about the need for a Phase 4 (post-marketing surveillance) study, bypassing Phase 3 if a pivotal Phase 2 leads directly to approval.

That AS is talking so much about a 'pivotal' or 'registrational' Phase 2 study in the US suggests that Avacta is in close discussion with the FDA and all that needs doing is to agree the details of the Phase 2 study based on the findings in the two Phase 1 Arms - not only has Avacta onboarded excellent clinical personnel, we've also got the FDA working with us.

I'm glad I don't live in your world Touk...

have you ever heard of 'evidence based medicine'?

Touk... please take the time to describe here your understanding of the characteristics of the diagnostics and the pharma industries and how they differ. Use interpretative dance if you like, posted to YouTube.

OK. A lot of green boxes. So...

My take home from the LFT fiasco was that Avacta's LFT was too expensive compared to the cheap chInese junk that the cheapskate Tory Govt were prepared to pay from the public coffers if some of it couldn't go to their mates and landlords (pub owners that is, not land owners, god forbid!)

Alan ssid as much (about the costs, not about cronyism) pre-pulling the LFT.

Given the 'encouraging data' from a long time back, any oncology-orientated pharma company worth its salt will have already set up a small project to road test the pre|CISION platform with their own cytotoxic-but-too-toxic research compounds (those with a free NH2 group). They can do this. What they cannot do is commercialise any of them without an agreement with Avacta (or a patent challenge).

So the question is, which leaving group to use? The AVA6000 one (5140 I think it is called) or the AVA3996 one (?). Or another one, either within the scope of the Bachovchin patents or without?

Better to look at MCap rather than SP I think.