Replies to post #305536 on Avid Bioservices Inc (CDMO)

[goodJohnhunting]

This is called, "endogenous protein cross reactivity".

In other words a lot of biologic competition for a clumsy therapeutic, IMO.

They could theoretically eliminate some competition by introducing specific statin combination that would reduce b2gp1 antigen presentation (from domain V2 epitope) to LDL receptor. Just saying..

Also, if ever a molecule needed exact PK data, this would be it.

All the best,
John

[Protector]

vinmantoo, CP is not wrong :)

I referenced the slides with the companies that have PS-receptor technology and the one from, I think it was Hitchins, with the increased list of PS receptors.

The statement was clear: Many immune cell PS-receptor types EXIST (not just the two most popular on this board because they find themselves on MDSC's and M2 Macrophages).

When PS exposes it are millions of molecules (a cell is about 5 nm in diameter and PS is only part of the bi-layer membrane. You can appreciate the scale we are talking about here.

Inevolution this exposed PS (actually part of apoptosis, the natural cell death cycle but here exposed because of the damage to endothelial cells lining the blood vessels, due to cancer tumours) is non-discriminatory. In other words it binds ALL type of PS receptors on cells it encounters and hence manages to CONDITION the TUMOUR ENVIRONMENT.

It actually says to all those cells: Whatever your role is in attacking damaged cells, please don't because the damage is of natural expected cause for dying cells.

And this PS message yell has EXACTLY the same meaning whether PS is exposed due to apoptosis or other cell damage of cancer/viral origin.

So making a DRUG that binds one type of PS receptor does NOT have that synchronised effect on the complete environment and all PS receptors that should receive the same message.

You'dd need to make a COMBO, or if you have the know-how a very large molecule with suitable domains varyity to bind them all (and size would work against you). The combo would be more likely then the later.

With Bavituximab or BetaBodies one circumvents all that and simply bind PdSer (the LIGAND alike concept in PS world that binds PS-R the PS receptors).

And actually what you are doing is killing the message from being communicated to the cell that hold PS-receptors.

As a CONSEQUENCE the immune-system cells DO NOT withhold their attack if they see cell damage (they no longer think it is normal) and the PD-1, CTLA-4 etc therapies can work better. At the SAME TIME the Fx-Gamma binding allows for immune response mechanisms that will prevent future relapse of the SAME condition. And that is because we did not only BLOCK PS from SUPPRESSING THE IMMUNE SYSTEM but we also STIMULATED the immune system (see cytokine action in Bavituximab's MoA).

However, EXCEPT if you have the results of the Yervoy+Bavituximab clinical trial or are privy to ANY OTHER source on Bavituximab combo's with IO that we would not have, it is IMO impossible for you to state

it explains why Bavi likely isn't a good anti-cancer target

But hey, I give you the word LIKELY. And by the way I we need a clinical trial to prove Bavi works with IO then you need one to prove it doesn't work with IO. And since there isn't any public data...at my knowledge.