Replies to post #177240 on Avid Bioservices Inc (CDMO)

[Protector]

Liver, the expectations are high, or not?

I know this title is a little controversial because some do not expect much from PPHM's Liver clinical trials, some have normal expectations and others think the liver results will be great, as were Lung and Breast results before.

In stead of digging in arguments such as that SK has high expectations, which as cheynew pointed out he had also for Pancreatic (which scored only a little above SOC unless ones would look into sub-sections), or just start from the assumption that until now we have ALWAYS beaten SOC small or big time and hence Bavi will do it again, I decided to try to substantiate the result anticipations.

Now I am not going to repeat the detailed mechanism (MOA) of Bavi as there are sufficient post on here that do. For the new reader just in a few lines: Bavituximab caps PS (Phosphatidylserine) each time a disease (cancer, viral,etc) or natural cell death exposes it to the outside of the cell where it is otherwise never found. By this capping PS can not suppress immune cells from activating the immune system at a systemic level and hence the cancer can progress/proliferate and flourish.

Liver cancer is a top 5 cancer (those rankings change as some countries economies change, detection improves and people's habits change) when it comes to occurrence but is VERY HARD the cure (Top 3).

So in order to try to substantiate this and relate it to Bavi I have set-up a very simple reasoning and started some research from there. I said:

Cancers flourish in "exposed PS" rich environments.

The reasoning behind the statement was simple; PS suppresses MDSCs and Macrophages from calling in the help of the immune system, so the more PS exposed the more Suppression and the more the tumour stands alone! As a consequence I look for PS rich areas of the body because they have the highest potential to expose PS because we know that PS exists only on the inside of the cell in normal circumstances and hence constitutes a natural reserve of PS to be exposed on damage/death of the involved cell types.

I think the above is pure logic about the potential which cannot be denied while of course it says nothing about whether that patential source of PS can also be equally well exposed. So we continue.

Factual data
So I started my search with PS and I found this:

PS can be found in meat, but is most abundant in the brain and in innards such as liver and kidney. Only small amounts of PS can be found in dairy products or in vegetables, with the exception of white beans.

Source: good old wiki will do for this
I add, from the above source Soy Lecithin (a substance found in Soya beans) as being on the Top Of The List, we'll come to that in a minute.

Reasoning
So, if PS is found more abundantly in the Liver cells, compared to Breast and Lungs cells, then it is fair to assume that there will be more PS exposure ones things go wrong with cells and that immune/inflammatory response activation is suppressed more intensively. And we will agree that a cancer fits the description of something going wrong with the cells, including the needed cell damage/death scenario needed for PS exposure, do we?

In the presence of liver cells that are richer in PS it is therefore logical to, even on pure statistical basis, say that such exposure will be proportional to the amount of PS per volume found in the cells. And hence the PS molecules will percentage wise be more present in the blood stream (incl. exosomes), on the cell surface, probably not in the tumour vascular endothelial cells, then it would be the case with say Lung or Breast cells.

As a consequence Bavi should be able to disturb the PS vs MDSCs & Macrophages balance more easily because it will have more opportunity to bind/cap larger amounts of PS and therefore be more effective percentage wise. And percentage wise is important because we know that the MDSCs and Macrophages must in sufficient numbers be able to send out there signalling substances without being suppressed by PS for the immune and inflammatory responses to occur.

One could ask the question if the Livers poor cell regeneration (compared to others in the body) is related to its PS richness.
If the Liver is a PS rich environment and actually a localized PS concentration enhancer and since MDSCs and Macrophages are a body wide blood substance that keep to a certain equipotential/solution (due to their charge distribution and the rapid flow of the blood) it is very probable that Liver PS largely outnumbers/overwhelms them and is therefore very efficient in protecting the tumour.


Liver Cancer and Asia
Soy lecithin is the most rich plant source of PS. Soya is consumed the most in Asia and Japan specifically is renowned to serve nothing without their famous soy-sauces. Japan is Liver Cancer country #1.

We have always been looking as the cell to be the source of PS and never to PS as a nutritive element. PS is used in sport nutrition and has a number of applications. But as a substance present in the blood it, without any doubt, contributes to inflammation/infection response activation suppression. Because again, the body does not discriminate because a Phosphatidylserine molecule is a Phosphatidylserine molecule.

So the Bavi's MOA starts to make more and more sense when we relate it to the daily behaviour and certainly nutritive habits of humans. A PS low diet looks like an extra factor to think about before, during an after the treatment of cancer patients. There goes soya-milk, soya butter, soya-pudding, etc :)


As a side note and something to think about
Also since the brain is PS king #1 one could ask what exactly it causes over there, being protected EXTRA behind the brain-blood barrier? What role could Bavi play there, possibly in combination with Cotara. Is that the path to future Alzheimer treatment?


Conclusion
The above would then explain why Bavituximab should be very efficient in Liver, and normally also in Kidney and Brain, cancers.


It may look simpler and simpler each day to connect new dots but we should never forget we thank this to Doctor Phil Thorpe and his colleagues.

And, I think I'll think twice before eating white beans with tomato sauce next time :) because they are the #2 plant-source of PS.

[geocappy1]

It has been stated several times that a patent clock starts ticking when it is applied for. We just had the discussion with BBs and Bungler made the statement as such. He made no mention of commercial product figuring in.