MGK_2—I think your insistence on apocalyptic prose and ALL CAPS tends to obscure rather than clarify. And quite a bit of the time I think you flat out get things wrong, and can’t even see it because you are so invested in that prose. Let me call you out on three examples from recent posts.
“Think of ctDNA as the “body count.” When tumor cells die, they burst and shed their DNA into the bloodstream.” (Post #160118)
Turns out tumor cells die in two ways… explosively bursting, and slowly fading away via apoptosis. Here’s something from Live Science Plus that describes this in more detail:
“Cancer treatments like chemotherapy kill tumor cells, often by pushing them to self-destruct, shrivel up and quietly die, or less commonly, by triggering a more explosive form of cell death.
Once the molecular switches that trigger apoptosis are flipped "on," the dying cell shrinks and bits of its membrane break away in "blebs." This causes the cells' internal components to leak out and attract phagocytes, which are immune cells responsible for gobbling up cellular debris.
The summoned phagocytes engulf the dead cancer cells and then break them down into smaller components, such as sugars and nucleic acids, the chain-like molecules found in DNA. Via this process, the dead cancer cells are recycled into components that can later be reused by other cells.”
https://www.livescience.com/health/cancer/wha...treatments
Now, you may say this is just semantics, or wordplay… WHAT DOES IT MATTER HOW THE TUMOR CELLS DIE? THEY”RE DEAD! But I think you would be missing important implications here… Apoptosis is part of how the immune system—even without the help of drugs—tries to deal with tumor cells. It relies on immune-system signaling, the turning on of that “molecular switch.” That’s easier on the body than cleaning up after exploding tumor cells. Would you rather have your tumors bursting and spreading debris all over the place, or shriveling up, getting gobbled up, and recycled? I’d say gobble gobble…
(Taking this further—and truth be told, this is just speculation on my part—the change from an M2 to an M1 phenotype that stimulates macrophages to eat and recycle circulating tumor cell debris is actually the biological means by which the ctDNA is reduced in the body. It’s not just a biomarker or a sign, it’s concrete evidence… the “thing itself.” Gobble, gobble, and recycle. Gobble gobble some more. It’s not “proof” of “Unmasking” or “Inversion…” It’s the way the immune system works to remove circulating tumor cells and thus reduce metastasis. And one of the responses of the tumor is to increase PD-L1. And of course leronlimab helps this process immeasurably… and patients do even better when you add an ICI. And that’s why we are all here).
You borrow the word “sketchy” from ScoreCarder to describe Cytodyn’s current cash flow situation… and that may be true in an absolute sense when compared to more established biotechs. But the recent agreement with Yorkville Advisors to sell up to $30 million worth of shares when Cytodyn wants to—that looks pretty good to me. Especially when we have what might very well be explosive data on the horizon. Great data/increased share price/limited dilution. Compared to the Paulson financing—well, we’re in a different league now. Out of the sketchy leagues, maybe not quite in the majors. Perhaps you haven’t recovered from the historical hangover from those Paulson days…
Let’s talk Merck. Like they don’t know about the patent cliff, and aren’t doing all kinds of billion-dollar deals and in-house development to jump that cliff? Qlex, the injectable? Done. Look at all the companies they've partnered with or bought out, and their Phase 3 pipeline in various cancers featuring Keytruda in combination with other drugs. Eisai (Lenvima—an oral kinase inhibitor), Astra-Zeneca (Lynparza—a PARP inhibitor), Moderna (V940—an mRNA vaccine), Kelun (MK-2870—an anti-TROP2 ADC and another ADC, sac-TMT), MK-1084 (in-house oral KRAS G12C inhibitor). Can’t forget about IMMP (LAG-3 agonist). Add the drugs Padcev (Astellas) and Welireg (in house) to that list. And add any reasonably promising cancer-biotech who wants to do combo trials with the best-selling drug in the world (often paid for by said biotechs). Yeah, I think it’s crazy to think Merck is looking at Cytodyn as their savior… like they are waiting on pins and needles for data from a penny stock biotech, with a checkered past, with a tiny data set (though it's getting larger all the time). We see it… but can they transcend their capital investments, sense of entitlement as the current top dog in cancer therapeutics, and hubris? I think you miss what is pretty obvious—they be dealing with the cliff, in a very calculated and risk-averse way, like a good corporate behemoth should.
It’s true they don’t have much in the pipeline for MSS CRC… which is the single biggest near-term reason they might be interested in Cytodyn at a reasonable price. But given the tens of billions they have invested in combo trials with existing and investigational drugs, and their partners… are they gonna pay us what we are worth, or what we want? Compared to other hungry Big Pharmas? They would have to write off those other investments, or slow-walk leronlimab to protect said investments, if they were to buy us out. The case for Merck is pretty weak in my eyes… but it always seems to be on the top of your list. Could happen… and I’ll eat crow if it does. But what you call “Advanced Pattern Recognition” I would call hopeful and insufficient due diligence. And while you are watching the Geography of the Exit… I’ll be watching the scans. And the ctDNA counts. And wondering who Dr. Lalezari’s friends and allies are--in positions of power--in Big Pharma. And the FDA.
Look, I don’t want to pile on anybody. But this is not some fucking academic exercise to me. Stage III locally advanced mssCRC. It was growing onto my bladder. An excellent surgeon took out two tumors, lopped off ten inches of my sigmoid colon, and was careful to preserve bladder function. Oxaliplatin and capecitabine took care of the rest… though genes and keeping in shape probably helped. No signs of cancer for the last 3.5 years—Yowza! Yeah, I shit two, sometimes three times a day—losing that much of your sigmoid colon tends to do that to a body. But my colonoscopies and CEA tests have come back great. No sign of disease. But you know… cancer has a way of coming back.
So listen up—I want as much clarity and insight I can get about this, not medical or metaphorical malfeasance and tortured prose searching for significance. Granted, there is some science in your work… hidden amongst the hyperbole, trying to escape the ALL CAPS that KEEP ON COMING AND NEVER LET UP. But I’m through trying to make sense of The Regulatory Moat and War Room Data and The Cure Coefficient and Clinical Physics and The Body Count—that’s all just noise. Cacophony instead of clarity. I have better things to do. All IMHO. Critique welcome.
“Think of ctDNA as the “body count.” When tumor cells die, they burst and shed their DNA into the bloodstream.” (Post #160118)
Turns out tumor cells die in two ways… explosively bursting, and slowly fading away via apoptosis. Here’s something from Live Science Plus that describes this in more detail:
“Cancer treatments like chemotherapy kill tumor cells, often by pushing them to self-destruct, shrivel up and quietly die, or less commonly, by triggering a more explosive form of cell death.
Once the molecular switches that trigger apoptosis are flipped "on," the dying cell shrinks and bits of its membrane break away in "blebs." This causes the cells' internal components to leak out and attract phagocytes, which are immune cells responsible for gobbling up cellular debris.
The summoned phagocytes engulf the dead cancer cells and then break them down into smaller components, such as sugars and nucleic acids, the chain-like molecules found in DNA. Via this process, the dead cancer cells are recycled into components that can later be reused by other cells.”
https://www.livescience.com/health/cancer/wha...treatments
Now, you may say this is just semantics, or wordplay… WHAT DOES IT MATTER HOW THE TUMOR CELLS DIE? THEY”RE DEAD! But I think you would be missing important implications here… Apoptosis is part of how the immune system—even without the help of drugs—tries to deal with tumor cells. It relies on immune-system signaling, the turning on of that “molecular switch.” That’s easier on the body than cleaning up after exploding tumor cells. Would you rather have your tumors bursting and spreading debris all over the place, or shriveling up, getting gobbled up, and recycled? I’d say gobble gobble…
(Taking this further—and truth be told, this is just speculation on my part—the change from an M2 to an M1 phenotype that stimulates macrophages to eat and recycle circulating tumor cell debris is actually the biological means by which the ctDNA is reduced in the body. It’s not just a biomarker or a sign, it’s concrete evidence… the “thing itself.” Gobble, gobble, and recycle. Gobble gobble some more. It’s not “proof” of “Unmasking” or “Inversion…” It’s the way the immune system works to remove circulating tumor cells and thus reduce metastasis. And one of the responses of the tumor is to increase PD-L1. And of course leronlimab helps this process immeasurably… and patients do even better when you add an ICI. And that’s why we are all here).
You borrow the word “sketchy” from ScoreCarder to describe Cytodyn’s current cash flow situation… and that may be true in an absolute sense when compared to more established biotechs. But the recent agreement with Yorkville Advisors to sell up to $30 million worth of shares when Cytodyn wants to—that looks pretty good to me. Especially when we have what might very well be explosive data on the horizon. Great data/increased share price/limited dilution. Compared to the Paulson financing—well, we’re in a different league now. Out of the sketchy leagues, maybe not quite in the majors. Perhaps you haven’t recovered from the historical hangover from those Paulson days…
Let’s talk Merck. Like they don’t know about the patent cliff, and aren’t doing all kinds of billion-dollar deals and in-house development to jump that cliff? Qlex, the injectable? Done. Look at all the companies they've partnered with or bought out, and their Phase 3 pipeline in various cancers featuring Keytruda in combination with other drugs. Eisai (Lenvima—an oral kinase inhibitor), Astra-Zeneca (Lynparza—a PARP inhibitor), Moderna (V940—an mRNA vaccine), Kelun (MK-2870—an anti-TROP2 ADC and another ADC, sac-TMT), MK-1084 (in-house oral KRAS G12C inhibitor). Can’t forget about IMMP (LAG-3 agonist). Add the drugs Padcev (Astellas) and Welireg (in house) to that list. And add any reasonably promising cancer-biotech who wants to do combo trials with the best-selling drug in the world (often paid for by said biotechs). Yeah, I think it’s crazy to think Merck is looking at Cytodyn as their savior… like they are waiting on pins and needles for data from a penny stock biotech, with a checkered past, with a tiny data set (though it's getting larger all the time). We see it… but can they transcend their capital investments, sense of entitlement as the current top dog in cancer therapeutics, and hubris? I think you miss what is pretty obvious—they be dealing with the cliff, in a very calculated and risk-averse way, like a good corporate behemoth should.
It’s true they don’t have much in the pipeline for MSS CRC… which is the single biggest near-term reason they might be interested in Cytodyn at a reasonable price. But given the tens of billions they have invested in combo trials with existing and investigational drugs, and their partners… are they gonna pay us what we are worth, or what we want? Compared to other hungry Big Pharmas? They would have to write off those other investments, or slow-walk leronlimab to protect said investments, if they were to buy us out. The case for Merck is pretty weak in my eyes… but it always seems to be on the top of your list. Could happen… and I’ll eat crow if it does. But what you call “Advanced Pattern Recognition” I would call hopeful and insufficient due diligence. And while you are watching the Geography of the Exit… I’ll be watching the scans. And the ctDNA counts. And wondering who Dr. Lalezari’s friends and allies are--in positions of power--in Big Pharma. And the FDA.
Look, I don’t want to pile on anybody. But this is not some fucking academic exercise to me. Stage III locally advanced mssCRC. It was growing onto my bladder. An excellent surgeon took out two tumors, lopped off ten inches of my sigmoid colon, and was careful to preserve bladder function. Oxaliplatin and capecitabine took care of the rest… though genes and keeping in shape probably helped. No signs of cancer for the last 3.5 years—Yowza! Yeah, I shit two, sometimes three times a day—losing that much of your sigmoid colon tends to do that to a body. But my colonoscopies and CEA tests have come back great. No sign of disease. But you know… cancer has a way of coming back.
So listen up—I want as much clarity and insight I can get about this, not medical or metaphorical malfeasance and tortured prose searching for significance. Granted, there is some science in your work… hidden amongst the hyperbole, trying to escape the ALL CAPS that KEEP ON COMING AND NEVER LET UP. But I’m through trying to make sense of The Regulatory Moat and War Room Data and The Cure Coefficient and Clinical Physics and The Body Count—that’s all just noise. Cacophony instead of clarity. I have better things to do. All IMHO. Critique welcome.
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