123, i was not criticizing Nader for "lack of knowledge".
Perhaps as important because perhaps it was not clear from my earlier posts, is that my take on this particular development of LL in the PD1/PDL1 pathway is bullish and not bearish for CYDY. So much so mind boggling bullish for me especially since I have never heard any mention of this possibility anywhere every before.
My comments were absolutely not intended as any criticism of Nader whatsoever.
When I said "Pourhassan can't possibly know about this", I was trying to articulate the following idea:
If Pourhassan knew that LL had a shot at completely replacing Keytruda and Opdivo, he would have suggested "quadruple digits" not "triple digits". (Of course, as some posters here have pointed out, maybe he did say "quadruple digits" in that latest proactive video!)
I have been following Cytodyn since March.
I have never heard anyone anywhere even suggest that Leronlimab could complement Keytruda and Oopdivo in the PDL1 pathway, let alone replace Keytruda and Opdivo!
Ohm suggested this possibility in 2019 but I didn't see it until now.
That one single pathway targeting that one single PD1 receptor is $15 billion dollars per year.
That's at least $100 billion in market cap.
$100 billion in market cap from one and only one pathway alone.
That's a 30x increase from today's share price.
$180 dollars per share.
So I will stand by my original point: Pourhassan does not know that there is a possibility that Leronlimab can influence the PD1/PDL1 pathway in the same fashion as Opdivo and Keytruda.
Because if he did, he would have said so. If he had this card, old poker face is not going to be able to keep it in his vest for long.
Now its certainly possible that I am wrong.
Maybe Pourhassan, Kelly, and the rest have studied the available experimental reports on leronlimab's suppression of PDL1 in cancer cells.
Maybe Pourhassan, Kelly, and the rest have decided that the experimental evidence for leronlimab's suppression of PDL1 expression in cancer cells is not strong enough to offer that disease indication publicly at this time.
My benchmark for what Nader/Kelly knows and what they say about is drawn from Cytodyn's public statements regarding Leronlimab application to Multiple Sclerosis.
Nader/Kelly have so, so strongly emphasized the possibility that LL could be effective in Multiple Sclerosis. The MS mouse results were offered as an epiphany.
When I heard the MS mouse result report, I asked myself "How hard is it to cure mice of Multiple Sclerosis?"
Turns probably at least a hundred research groups have cured mice of multiple sclerosis.
The particulars of multiple sclerosis in mice are not hard to work out. Its been going on for decades. Inject some mice with myelin oligodendrocyte protein. The injection causes an immune response against the injected protein. The injected protein is expressed on the surface of myelin cells in the brain. The stimulated immune response causes destruction of these myelin cells in the mouse brain, and thus you have a model for auto-immune destruction of myelin cells in human brains. The exact name for this phenomenon in mice is Experimental Autoimmune Encephalopathy, or EAE. EAE only happens in mice, and it only happens in these experiments when you inject the mice.
So it turns out that probably at least a hundred research groups have cured the EAE mice.
But very, very few drugs are available for the treatment of MS in humans and none are remotely close to a cure.
Probably I dont have all the facts. Maybe the mouse MS cure publicized by Cytodyn is somehow superior to the mouse MS cures achieved by many other researchers.
Even the most cursory google scholar search on EAE quickly turns up many articles on mouse MS cures. In fact, the same search turns up many articles entitled "Why do mouse MS cures always fail in humans?" or similar.
So it seems to me that the Cytodyn guys must be well aware that MS cures in mice are a dime a dozen, lots of people can do it, and the fact that you did it is not that big a deal.
So it strikes me that if the Cytody guys know this, and surely they must, then either the Cytodyn mouse MS cure is run-of-the-mill same as the rest or its superior and Cytodyn is keeping quiet about the superiority.
Again, my sense is that Cytodyn doesn't keep quiet about LL disease indications.
So when I observe Cytodyn pushing the mouse EAE experiment and keeping quiet about some elses CCR5 PD1/PDL1 experiment, I conclude that Pourhassan does not yet know about the CCR5 PD1/PDL1.
To my mind, the CCR5 PD1/PDL1 experiment is far more persuasive than the Cytodyn mouse EAE experiment.
Curing mice of EAE is relatively easy, biotech-wise.
Another thing that's relatively easy is creating a monoclonal antibody. Perhaps as many as one thousand research groups around the globe are capable of creating a monoclonal antibody.
What was difficult in the case of Opdivo and Keytruday is figuring out to hit the PD1 receptor.
But now they have it figured out and the run rate is $15 billion per year.
The function of that antibody is pathetically simple. Keytruda and Opdivo mabs bind to the PD1 receptor and that blocks PD1 signalling and that helps a great many cancer patients.
And then this totally insane experimental report posted by ohm.
Leronlimab blocks production of PDL1 in cancer cells.
This is totally crazy.
PDL1 is the molecule that is blocked by Keytruda and Opdivo from binding PD1 receptors. PDL1 expression by cancer cells is the whole and entire reason for existence of Keytrudy and Opdivo.
And now it seems Leronlimab might work on the other end of the pathway by preventing PDL1 being created?
Why in heavens name should LL have an effect in suppressing PDL1 expression in cancer cells in addition to LL's other known MOA's of t-cell chemotaxis, cancer cell chemotaxis, and macrophage repolarization?
It seems to me that Leronlimab involvement in the PD1/PDL1 pathway is far more significant that curing EAE in mice.
So again I am left with the conclusion that Pourhassan/Kelly just haven't been alerted to this possibility.
Certainly seems to me at least as important.
And, 123kidc, you were certainly absolutely right as to who it is that doesn't have a clue about Leronlimab MOA, its me.
Just to make sure we are clear on this, the person who doesn't have a clue about Leronlimab MOA is me. There is no doubt about that.
And that's fine with me. I don't mind being clueless. Especially when others are generous enough to educate me. When others are so generous as to educate, being clueless is a gift.
And that's where I see a thread that ties the whole leronlimab story together.
Perhaps I am not the only clueless person as to the MOA of Leronlimab.
We know with 100% certainty that Leronlimab's inventors were completely and totally clueless despite years of work on CCR5.
For more than a decade, the PR0140 journal articles always included some commentary to the effect that "signalling functions of CCR5 were not effected by binding of leronlimab to CCR5". In pretty much all of these experimental reports, the data did not really support the idea that CCR5 signalling was unaffected by leronlimab, but the PRO140 researchers needed LL safety indicators for HIV treatment, so they were always biased towards "Leronlimab binding to CCR5 has no effect on CCR5 signalling". Of course during this more than a decade of work on PRO140/CCR5, the researchers had no idea what the function of CCR5 was in the first place so it probably wasn't too hard to conclude LL had no effect. Its only in the last five years when everyone and their broterh starts publishing CCR5 articles on cancer, CNS disease, and others. Kabonk has posted some details on the odd PRO140 mantra of "no effect on CCR5 signalling" here on IV if anyone wants to read more.
So back again to why I feel i have no clue as to the MOA of leronlimab, and why MOA cluelessness might be relevant to Keytruda/Opdivo.
Its easy to find experimental reports of the following:
1) CCR5 blockade affects migration of immune cells
2) CCR5 blockade affects migration/metatastis of cancer cells
3) CCR5 affects macrophage polarization/repolarization
4) CCR5 expression correlates with cancer progression
But what are the mechanics of these situations? Cell migration is measured with microscopes and petri dishes. The experimenters literally watch the cells chase around after CCL5 and other chemicals. There are youtube videos of the cells chasing around. CCR5 expression measurement in cancer cells is get a bunch of cells, put them through the flow cytometer and see how many have CCR5.
And how about CNS? The EAE mice were cured. We know that leronlimab got across the blood/brain barrier, but we don't even know if LL travelled by itself, piggybacked on some t-cell travellers, or maybe even was important only for signalling and not for travelling.
So all this stuff is thought to be known about LL MOA, but how do the molecules actually talk to each other? What exactly is the pathway that is going on with these cells chasing around all over the place? I have no clue.
But not so with Keytruda/Opdivo and their $15 billion annual sales. The clues are few but absolute.
PD1 blockade means the T-cell will keep on hunting and killing.
Cancer cells secrete PDL1 protein into the bloodstream where it binds to the PD1 receptor which stops the T-cell from hunting and killing.
And, last but not least, in the experiment posted by ohm, CCR5 antagonism by maraviroc suppresses PDL1 secretion by cancer cells.
And there are a few other things that we know for certain. Bristol Meyers Squibb is runing a combo therapy trial for Opdivo and BMS813160 (spelling?), which is a CCR5 antagonist. So Bristol Meyers Squibb is testing in humans the theory that CCR5 is involved in the PD1/PDL1 pathway. Of course Opdivo is a Bristol Meyers Squibb product.
As as to 123kidc's lamentation that I seem to need a great deal of correction, that is certainly spot on as well.
I am very, very grateful for all the corrections that posters have provided.
I can only dream that this post contributes as much to my education as did my last
For sure I still don't understand a ton of stuff. I don't understand how the PRO140 researchers could work for a decade without figuring out the possibly massive importance of CCR5. I don't understand how CCR5 is involved in all these cells chasing around every which way. I don't understand how CCR5 is involved in macrophage polarization.
I am drawn to the conclusion that the PRO140 researchers didn't figure out the purpose of CCR5 because its really hard to figure out. I am drawn to the conclusion that its hard to figure out cuz it does some really weird stuff that doesn't leave a protein footprint. When humans walk the footprints are often clear as day. Not so much for cell footprints.
Perhaps as important because perhaps it was not clear from my earlier posts, is that my take on this particular development of LL in the PD1/PDL1 pathway is bullish and not bearish for CYDY. So much so mind boggling bullish for me especially since I have never heard any mention of this possibility anywhere every before.
My comments were absolutely not intended as any criticism of Nader whatsoever.
When I said "Pourhassan can't possibly know about this", I was trying to articulate the following idea:
If Pourhassan knew that LL had a shot at completely replacing Keytruda and Opdivo, he would have suggested "quadruple digits" not "triple digits". (Of course, as some posters here have pointed out, maybe he did say "quadruple digits" in that latest proactive video!)
I have been following Cytodyn since March.
I have never heard anyone anywhere even suggest that Leronlimab could complement Keytruda and Oopdivo in the PDL1 pathway, let alone replace Keytruda and Opdivo!
Ohm suggested this possibility in 2019 but I didn't see it until now.
That one single pathway targeting that one single PD1 receptor is $15 billion dollars per year.
That's at least $100 billion in market cap.
$100 billion in market cap from one and only one pathway alone.
That's a 30x increase from today's share price.
$180 dollars per share.
So I will stand by my original point: Pourhassan does not know that there is a possibility that Leronlimab can influence the PD1/PDL1 pathway in the same fashion as Opdivo and Keytruda.
Because if he did, he would have said so. If he had this card, old poker face is not going to be able to keep it in his vest for long.
Now its certainly possible that I am wrong.
Maybe Pourhassan, Kelly, and the rest have studied the available experimental reports on leronlimab's suppression of PDL1 in cancer cells.
Maybe Pourhassan, Kelly, and the rest have decided that the experimental evidence for leronlimab's suppression of PDL1 expression in cancer cells is not strong enough to offer that disease indication publicly at this time.
My benchmark for what Nader/Kelly knows and what they say about is drawn from Cytodyn's public statements regarding Leronlimab application to Multiple Sclerosis.
Nader/Kelly have so, so strongly emphasized the possibility that LL could be effective in Multiple Sclerosis. The MS mouse results were offered as an epiphany.
When I heard the MS mouse result report, I asked myself "How hard is it to cure mice of Multiple Sclerosis?"
Turns probably at least a hundred research groups have cured mice of multiple sclerosis.
The particulars of multiple sclerosis in mice are not hard to work out. Its been going on for decades. Inject some mice with myelin oligodendrocyte protein. The injection causes an immune response against the injected protein. The injected protein is expressed on the surface of myelin cells in the brain. The stimulated immune response causes destruction of these myelin cells in the mouse brain, and thus you have a model for auto-immune destruction of myelin cells in human brains. The exact name for this phenomenon in mice is Experimental Autoimmune Encephalopathy, or EAE. EAE only happens in mice, and it only happens in these experiments when you inject the mice.
So it turns out that probably at least a hundred research groups have cured the EAE mice.
But very, very few drugs are available for the treatment of MS in humans and none are remotely close to a cure.
Probably I dont have all the facts. Maybe the mouse MS cure publicized by Cytodyn is somehow superior to the mouse MS cures achieved by many other researchers.
Even the most cursory google scholar search on EAE quickly turns up many articles on mouse MS cures. In fact, the same search turns up many articles entitled "Why do mouse MS cures always fail in humans?" or similar.
So it seems to me that the Cytodyn guys must be well aware that MS cures in mice are a dime a dozen, lots of people can do it, and the fact that you did it is not that big a deal.
So it strikes me that if the Cytody guys know this, and surely they must, then either the Cytodyn mouse MS cure is run-of-the-mill same as the rest or its superior and Cytodyn is keeping quiet about the superiority.
Again, my sense is that Cytodyn doesn't keep quiet about LL disease indications.
So when I observe Cytodyn pushing the mouse EAE experiment and keeping quiet about some elses CCR5 PD1/PDL1 experiment, I conclude that Pourhassan does not yet know about the CCR5 PD1/PDL1.
To my mind, the CCR5 PD1/PDL1 experiment is far more persuasive than the Cytodyn mouse EAE experiment.
Curing mice of EAE is relatively easy, biotech-wise.
Another thing that's relatively easy is creating a monoclonal antibody. Perhaps as many as one thousand research groups around the globe are capable of creating a monoclonal antibody.
What was difficult in the case of Opdivo and Keytruday is figuring out to hit the PD1 receptor.
But now they have it figured out and the run rate is $15 billion per year.
The function of that antibody is pathetically simple. Keytruda and Opdivo mabs bind to the PD1 receptor and that blocks PD1 signalling and that helps a great many cancer patients.
And then this totally insane experimental report posted by ohm.
Leronlimab blocks production of PDL1 in cancer cells.
This is totally crazy.
PDL1 is the molecule that is blocked by Keytruda and Opdivo from binding PD1 receptors. PDL1 expression by cancer cells is the whole and entire reason for existence of Keytrudy and Opdivo.
And now it seems Leronlimab might work on the other end of the pathway by preventing PDL1 being created?
Why in heavens name should LL have an effect in suppressing PDL1 expression in cancer cells in addition to LL's other known MOA's of t-cell chemotaxis, cancer cell chemotaxis, and macrophage repolarization?
It seems to me that Leronlimab involvement in the PD1/PDL1 pathway is far more significant that curing EAE in mice.
So again I am left with the conclusion that Pourhassan/Kelly just haven't been alerted to this possibility.
Certainly seems to me at least as important.
And, 123kidc, you were certainly absolutely right as to who it is that doesn't have a clue about Leronlimab MOA, its me.
Just to make sure we are clear on this, the person who doesn't have a clue about Leronlimab MOA is me. There is no doubt about that.
And that's fine with me. I don't mind being clueless. Especially when others are generous enough to educate me. When others are so generous as to educate, being clueless is a gift.
And that's where I see a thread that ties the whole leronlimab story together.
Perhaps I am not the only clueless person as to the MOA of Leronlimab.
We know with 100% certainty that Leronlimab's inventors were completely and totally clueless despite years of work on CCR5.
For more than a decade, the PR0140 journal articles always included some commentary to the effect that "signalling functions of CCR5 were not effected by binding of leronlimab to CCR5". In pretty much all of these experimental reports, the data did not really support the idea that CCR5 signalling was unaffected by leronlimab, but the PRO140 researchers needed LL safety indicators for HIV treatment, so they were always biased towards "Leronlimab binding to CCR5 has no effect on CCR5 signalling". Of course during this more than a decade of work on PRO140/CCR5, the researchers had no idea what the function of CCR5 was in the first place so it probably wasn't too hard to conclude LL had no effect. Its only in the last five years when everyone and their broterh starts publishing CCR5 articles on cancer, CNS disease, and others. Kabonk has posted some details on the odd PRO140 mantra of "no effect on CCR5 signalling" here on IV if anyone wants to read more.
So back again to why I feel i have no clue as to the MOA of leronlimab, and why MOA cluelessness might be relevant to Keytruda/Opdivo.
Its easy to find experimental reports of the following:
1) CCR5 blockade affects migration of immune cells
2) CCR5 blockade affects migration/metatastis of cancer cells
3) CCR5 affects macrophage polarization/repolarization
4) CCR5 expression correlates with cancer progression
But what are the mechanics of these situations? Cell migration is measured with microscopes and petri dishes. The experimenters literally watch the cells chase around after CCL5 and other chemicals. There are youtube videos of the cells chasing around. CCR5 expression measurement in cancer cells is get a bunch of cells, put them through the flow cytometer and see how many have CCR5.
And how about CNS? The EAE mice were cured. We know that leronlimab got across the blood/brain barrier, but we don't even know if LL travelled by itself, piggybacked on some t-cell travellers, or maybe even was important only for signalling and not for travelling.
So all this stuff is thought to be known about LL MOA, but how do the molecules actually talk to each other? What exactly is the pathway that is going on with these cells chasing around all over the place? I have no clue.
But not so with Keytruda/Opdivo and their $15 billion annual sales. The clues are few but absolute.
PD1 blockade means the T-cell will keep on hunting and killing.
Cancer cells secrete PDL1 protein into the bloodstream where it binds to the PD1 receptor which stops the T-cell from hunting and killing.
And, last but not least, in the experiment posted by ohm, CCR5 antagonism by maraviroc suppresses PDL1 secretion by cancer cells.
And there are a few other things that we know for certain. Bristol Meyers Squibb is runing a combo therapy trial for Opdivo and BMS813160 (spelling?), which is a CCR5 antagonist. So Bristol Meyers Squibb is testing in humans the theory that CCR5 is involved in the PD1/PDL1 pathway. Of course Opdivo is a Bristol Meyers Squibb product.
As as to 123kidc's lamentation that I seem to need a great deal of correction, that is certainly spot on as well.
I am very, very grateful for all the corrections that posters have provided.
I can only dream that this post contributes as much to my education as did my last
For sure I still don't understand a ton of stuff. I don't understand how the PRO140 researchers could work for a decade without figuring out the possibly massive importance of CCR5. I don't understand how CCR5 is involved in all these cells chasing around every which way. I don't understand how CCR5 is involved in macrophage polarization.
I am drawn to the conclusion that the PRO140 researchers didn't figure out the purpose of CCR5 because its really hard to figure out. I am drawn to the conclusion that its hard to figure out cuz it does some really weird stuff that doesn't leave a protein footprint. When humans walk the footprints are often clear as day. Not so much for cell footprints.
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