Member Info for RorkesDrift

Are you suggesting this is a mock up?

No actual pictures of them on the stand which is odd. I'm still not convinced by the diagram. Spooling orrors slip through (reprint or not) but PDF on website is standard especially if you are not going to ring Timster back

What do you think of shadows on final.page?

https://youtu.be/JTTC_fD598A

You know you want to....

That wooden surprise me

Is it September?

Say it Timster. Say it for me.....

How I long for a ..........

Is it the virus binds to AB with signal attached, flows down to a line of affimers which then also bind the virus. So using ABs and affimers ?

Timster suspects the mole catcher?

Not sure I understand the diagram "test principle". Confused as to what initially binds the virus (is it AB or affimer). Words and pictures don't match. Might have misinterpreted it.

Couple of things. The stated timeline for Ava006 is results by end Q1. That would mean cohort 2 before xmas. AS has said in last update he would RNS cohort 2.

He hasn't but that could be he has just changed his mind. We have company update before Xmas and maybe that is deemed a better place.

Thank you cool free.

All have almost exactly the same number of posts. Its as if someone batch processes profiles.

The Ava004 is described by Avacta has a backbone of potentially many different conjugates. It has a much longer half life meaning less frequent dosing and even the possibility of sub cutaneous (at home - see insulin) dosing.

It has been very quiet on the Ava004 but given the post yesterday maybe Avacta are ready to go to next stage.

They also have two programmes ongoing with LG and Modern a for over 5 years. Perhaps one of these is the Avastin lookalike but that is yet another string to the bow. I have a feeling that a Nasdaq fund raise is on the way - so much to go at and resources are tight - LFD underwriting probably not going to be enough now. Last one was at £1.20 but Ava006 news IF good would see this raise at a much higher level - mid 2022. Alternatives are partnerships or jeez maybe someone just makes an offer. Timing is key - need a lot more in shop window but jeez what a window it could be this time next year.

Resist I must resist. (I won't mention standard biotech early stage risks).

Worth checking out this too

https://www.genengnews.com/insights/antibody-mimetics/

To be fair I googled most of it.

Suspect we will also hear about AVA004 at next update. This was put on hold in favour of AVA006 which had lower risk. Was meant to progress to clinic in 2020 and 2021 but maybe Avacta will find a way of reigniting.

Then there is the US and LFD - regulatory authorities look to each other. My guess is pre-Xmas.

Immunology is complicated and you need to take my interpretation with caution. Ive had ti simplify it in my own mind.

T-cells kill other cells. They do thus by recognising problems with other cells - perhaps they have viral proteins jutting through their surface. Some T-cells only attack cells if they have a specific protein (antigen) present.

T-cells interact with other cells though. So cells can "turn off" T-cells by binding to a receptor on the T-cell surface.  This t-cell receptor is PD-1. The cell does this by producing the protein PD-L1.

PD-L1 is highly expressed on certain tumors reducing activation of T-cells that recognize and attack the cancer. The cancer survives because it turns T-cells off.

By turning PD-L1 off this inhibition of T-cells is turned off. Inhibit the off switch?

Many PD-L1 inhibitors are in development as immuno-oncology therapies and are showing good results in clinical trials. 
Some are on the market durvalumab atezolizumab and avelumab

Talabostat stimulates the upregulation of cytokines and chemokines - chemicals involved in activating our bodies immune responses. I think it also inhibits FAP which is actually one way it has an anti tumour effect. The reliance on Precision (fap clevage) is therefore odd but my take is Avacta have bound only one part of the Talabostat molecule.

In terms of benefit Talabostat development was held back due to its toxicity but it did work against cancer.

So we go back to Precision targets high FAP normaly associated with tumours. Therefore tumour environment has high levels of drug whilst rest of body is spared. By attaching PDL1 recognition the targeting is further enhanced - synergistic.

Recyclable

Slight modification for the presentation at start of this month. I'm guessing we will hear more in Annual report but looks like Avacta on fishing trip for a partner - no way do they have enough resources to go alone (please no more dilution unless well North of £1.20).

Since tablostat inhibits FAP they emphasise its the active VpB that is attached. If Ava006 establishes FAP concept then TMAC also gets a boost - not just Avacta Velcade. $60M milestone payments could be enough

https://www.pegsummiteurope.com/antibody-drug-conjugates

IMPROVING THE SAFETY, EFFICACY AND STABILITY OF ADCs
10:35
Novel Approaches to Modulate the TME with Immuno-Modulatory Combination Therapies, with Improved Safety and Efficacy in Mice

Amrik Basran, PhD, CSO, Avacta Life Sciences
By combining our anti-PD-L1 Affimer antagonist (AVA04 Fc) with a potent, small-molecule inducer of the innate immune system (Val-Boro-Pro, VbP), we have demonstrated full tumour regression in mouse syngeneic models with an immunological memory effect in several individuals. We have developed an Affimer-drug conjugate (TMAC) that included a novel FAP-a cleavable linker which is preferentially cleaved in the TME, which showed significant anti-tumour effects in a CT26 syngeneic model and reduced the toxicity profile for VbP.

Short communication in Research Journal of the Nervous system vol 5 number 51. Author is Avacta CSO

"The Affimer platform is an antibody mimetic scaffold based on the human protease inhibitor, Stefin A and we have
generated a range of antagonists against several key checkpoints such PD-L1. With our anti-PDL1 Affimer Fc we have
demonstrated total tumour regression in mouse syngeneic models in combination with Talabostat and immunity to
rechallenge with tumour cells, showing that we have achieved an immune memory response. Conjugating Talabostat to
an Affimer antagonist using a novel FAP-alpha cleavable linker (TMAC™), we have demonstrated tolerability and efficacy
in mouse syngeneic models."

This looks a lot like the work being done by bioxcel. It also highlights avactas anti pdl1 - two products - with and without the talobostat linker.