Ken--a couple weeks ago you were talking with TechGuru about PD-L1 numbers and that we will see them October 19 at ESMO. You went on to say that's great "...Since that's really what the CLOVER trial is about: how many patients who were not candidates for ICI treatment before receiving Leron can now be treated with an ICI."
I think with the April data drop--and Dr Jay's recent comments--that perspective can be put aside for the next few months as the CLOVER trial rolls on and, at the least, challenges that perspective. It may very well end up that being paired with an ICI might be leronlimab's best-use/best-case scenario in cancer... but I am beginning to question that. The ICI pairing doesn't begin to capture leronlimab's profound effects on cutting down metastasis and improvement in the day-to-day overall health of cancer patients. Not to mention leronlimab's apparent synergy with Avastin and Lonsurf in mCRC. And there are implications for leronlimab's development and worth--like, the quickest path to market, and the overall benefits that leronlimab brings to patient care in cancer--that remain to be "adjudicated". So I thought I'd dive in and explore some of those implications.
Now, the possibility of curing cancer ala the Ladies of Leronlimab outta trump anything out there, yes? But what if the prime and pair scenario works in TNBC but not in mCRC? Not in NSCLC? Not in some cancers but works in others? There is a great deal of testing to be done before we say that leronlimab and an ICI is a universal cure... Though a new basket trial with an ICI would answer many of those questions.
Here's the thing--while we wait on those trials to begin and mature... we could be actually selling leronlimab in 2027 as part of the SOC for mCRC. The FDA would have to cooperate, and it would also be nice to have Genetech/Roche or Taiho Pharmaceuticals onboard to help with sales... but if the data in mCRC are as good as the ctDNA numbers imply, leronlimab's quickest route to market might very well be as an add-on to the SOC in 3rd or 4th-line mCRC. No ICI at all in this scenario (though if any patients progress in the trial, we should be hearing about ICI treatment come rollover time).
If Cytodyn wanted to prove the prime-and-pair thesis, why didn't they just initiate a Phase 2 trial in TNBC with an ICI back in 2024 or 25? I honestly do not know why they didn't do this when the news broke about the 5 Ladies... That's what I would have done (See cancer--kill it!). But the Cytodyn brain trust figured mCRC was the way to go. Can't really call them out for this, given the early CLOVER results... And of course 3 out of 4 CRC patients given LL and chemo in the basket trial getting a Partial Result or better must have been part of the thought process. And, did you know, Cytodyn was given approval by the FDA for a Phase 2 trial in mCRC with LL and regorafenib back in 2019 (regorafenib was part of an earlier SOC). So Cytodyn has been jonesing for 5-6 years to get leronlimab into mCRC patients... for reasons that have nothing to do with pairing with an ICI.
The second major reason I believe Cytodyn is right to explore the anti-cancer benefits of leronlimab without an ICI is because turning cold tumors hot is the holy grail for immune-oncology companies, and several seem close. ONCY and AGEN have been brought up in this space, and I would add KZIA and the cancer vaccines (Merck, mRNA, BioNTech) to that list. By 2030 I suspect a couple more companies--along with Cytodyn--will be able to justifiably claim they turn cold tumors hot. And if the thesis of the Oct 25 Nature article is proven--that those receiving an ICI do much better when paired with a covid vaccine that energizes their immune system--then leronlimab would just be more expensive then a covid shot, even if it brings much more to the table than any other drug that turns cold tumors hot. And this would mean a great deal of testing to figure out which drug works best, on which kind of cancers. So there will most likely be a great deal of competition in this space, and soon. Now, leronlimab might very well be the best drug out there to turn tumors hot... But there will be much testing in various indications to sus this out. I want more immediate results. Like CLOVER can provide--without an ICI.
Two comments, and then I'll let AI have the final word. In the Picasso trial, maraviroc and an ICI didn't do shit in MSS mCRC. Something like a 5% ORR. Leronlimab is a much more effective CCR5 inhibitor than maraviroc... but maybe CCR5 inhibitors don't work very well with ICIs in mCRC. We don't really know--the lack of studies. But we are soon going to find out just how special a four-leaf leronlimab really is. The second thing is, if we can pull out some data from CLOVER that proves--or hints strongly--that leronlimab eliminate metastasis... well, that would be pretty darn significant. Is metastasis a RANTES disease? We can't really prove that if leronlimab and an ICI just wipe out cancer entirely... with all the Big Guys at Merck and Roche claiming it was their ICI that did the heavy lifting. So Ken--I don't think the be all and end all of leronlimab is all about pairing with an ICI. For a TNBC patient--probably yes. For an mCRC patient? Well, we are about to find out. And the mCRC market is much larger than the TNBC market... So there is that. I'm gonna say the brain-trust at Cytodyn made the right call. ICI--take a seat for a bit. You and leronlimab may be the universal cure for cancer. We will find out soon enough. But there are other things to know about this drug that may save many lives in here-to-for unknowable ways.
The above was thought-out without reference to AI. But I just had to ask...
"[color=var(--text)]Looking at the broader landscape of executive commentary, scientific presentations, and investor sentiment across specialized networks, we can map out a distinct clinical trajectory for leronlimab completely independent of checkpoint inhibitors:[/color]
• First-Line Maintenance Positioning: If the final CLOVER data mirrors the early stable disease metrics, CytoDyn will likely push leronlimab out of the refractory "late-line" setting and position it as a first-line or second-line maintenance therapy. Layering leronlimab into early SOC regimens could theoretically delay or entirely block metastasis from ever developing.
• The ctDNA-Driven Accelerated Approval Strategy: Armed with the Natera Signatera partnership data, CytoDyn may try to bypass long overall survival (OS) timelines by petitioning the FDA for an accelerated approval pathway based on molecular response kinetics (rapid ctDNA clearance). If a 70% ctDNA drop at Week 2 correlates heavily with long-term progression-free survival, regulators may grant a conditional window.
[color=var(--text)]• Tumor-Agnostic "TME-Disruptor" Labels: Because CCR5 over-expression is a universal mechanism for solid tumor metastasis, CytoDyn's success in CRC without an ICI lays the groundwork for a tumor-agnostic label. They could market leronlimab as a universal adjuvant to be added to any standard chemotherapy backbone for aggressive solid tumors (breast, pancreatic, prostate) simply to amplify the base chemo's payload capacity."[/color]
All due respect, Ken. But on this particular point, I'm gonna say you are dead wrong. The CLOVER trial is settling once and for all that we don't need an ICI to prove our worth in cancer. And that is going to be... priceless.
I think with the April data drop--and Dr Jay's recent comments--that perspective can be put aside for the next few months as the CLOVER trial rolls on and, at the least, challenges that perspective. It may very well end up that being paired with an ICI might be leronlimab's best-use/best-case scenario in cancer... but I am beginning to question that. The ICI pairing doesn't begin to capture leronlimab's profound effects on cutting down metastasis and improvement in the day-to-day overall health of cancer patients. Not to mention leronlimab's apparent synergy with Avastin and Lonsurf in mCRC. And there are implications for leronlimab's development and worth--like, the quickest path to market, and the overall benefits that leronlimab brings to patient care in cancer--that remain to be "adjudicated". So I thought I'd dive in and explore some of those implications.
Now, the possibility of curing cancer ala the Ladies of Leronlimab outta trump anything out there, yes? But what if the prime and pair scenario works in TNBC but not in mCRC? Not in NSCLC? Not in some cancers but works in others? There is a great deal of testing to be done before we say that leronlimab and an ICI is a universal cure... Though a new basket trial with an ICI would answer many of those questions.
Here's the thing--while we wait on those trials to begin and mature... we could be actually selling leronlimab in 2027 as part of the SOC for mCRC. The FDA would have to cooperate, and it would also be nice to have Genetech/Roche or Taiho Pharmaceuticals onboard to help with sales... but if the data in mCRC are as good as the ctDNA numbers imply, leronlimab's quickest route to market might very well be as an add-on to the SOC in 3rd or 4th-line mCRC. No ICI at all in this scenario (though if any patients progress in the trial, we should be hearing about ICI treatment come rollover time).
If Cytodyn wanted to prove the prime-and-pair thesis, why didn't they just initiate a Phase 2 trial in TNBC with an ICI back in 2024 or 25? I honestly do not know why they didn't do this when the news broke about the 5 Ladies... That's what I would have done (See cancer--kill it!). But the Cytodyn brain trust figured mCRC was the way to go. Can't really call them out for this, given the early CLOVER results... And of course 3 out of 4 CRC patients given LL and chemo in the basket trial getting a Partial Result or better must have been part of the thought process. And, did you know, Cytodyn was given approval by the FDA for a Phase 2 trial in mCRC with LL and regorafenib back in 2019 (regorafenib was part of an earlier SOC). So Cytodyn has been jonesing for 5-6 years to get leronlimab into mCRC patients... for reasons that have nothing to do with pairing with an ICI.
The second major reason I believe Cytodyn is right to explore the anti-cancer benefits of leronlimab without an ICI is because turning cold tumors hot is the holy grail for immune-oncology companies, and several seem close. ONCY and AGEN have been brought up in this space, and I would add KZIA and the cancer vaccines (Merck, mRNA, BioNTech) to that list. By 2030 I suspect a couple more companies--along with Cytodyn--will be able to justifiably claim they turn cold tumors hot. And if the thesis of the Oct 25 Nature article is proven--that those receiving an ICI do much better when paired with a covid vaccine that energizes their immune system--then leronlimab would just be more expensive then a covid shot, even if it brings much more to the table than any other drug that turns cold tumors hot. And this would mean a great deal of testing to figure out which drug works best, on which kind of cancers. So there will most likely be a great deal of competition in this space, and soon. Now, leronlimab might very well be the best drug out there to turn tumors hot... But there will be much testing in various indications to sus this out. I want more immediate results. Like CLOVER can provide--without an ICI.
Two comments, and then I'll let AI have the final word. In the Picasso trial, maraviroc and an ICI didn't do shit in MSS mCRC. Something like a 5% ORR. Leronlimab is a much more effective CCR5 inhibitor than maraviroc... but maybe CCR5 inhibitors don't work very well with ICIs in mCRC. We don't really know--the lack of studies. But we are soon going to find out just how special a four-leaf leronlimab really is. The second thing is, if we can pull out some data from CLOVER that proves--or hints strongly--that leronlimab eliminate metastasis... well, that would be pretty darn significant. Is metastasis a RANTES disease? We can't really prove that if leronlimab and an ICI just wipe out cancer entirely... with all the Big Guys at Merck and Roche claiming it was their ICI that did the heavy lifting. So Ken--I don't think the be all and end all of leronlimab is all about pairing with an ICI. For a TNBC patient--probably yes. For an mCRC patient? Well, we are about to find out. And the mCRC market is much larger than the TNBC market... So there is that. I'm gonna say the brain-trust at Cytodyn made the right call. ICI--take a seat for a bit. You and leronlimab may be the universal cure for cancer. We will find out soon enough. But there are other things to know about this drug that may save many lives in here-to-for unknowable ways.
The above was thought-out without reference to AI. But I just had to ask...
"[color=var(--text)]Looking at the broader landscape of executive commentary, scientific presentations, and investor sentiment across specialized networks, we can map out a distinct clinical trajectory for leronlimab completely independent of checkpoint inhibitors:[/color]
• First-Line Maintenance Positioning: If the final CLOVER data mirrors the early stable disease metrics, CytoDyn will likely push leronlimab out of the refractory "late-line" setting and position it as a first-line or second-line maintenance therapy. Layering leronlimab into early SOC regimens could theoretically delay or entirely block metastasis from ever developing.
• The ctDNA-Driven Accelerated Approval Strategy: Armed with the Natera Signatera partnership data, CytoDyn may try to bypass long overall survival (OS) timelines by petitioning the FDA for an accelerated approval pathway based on molecular response kinetics (rapid ctDNA clearance). If a 70% ctDNA drop at Week 2 correlates heavily with long-term progression-free survival, regulators may grant a conditional window.
[color=var(--text)]• Tumor-Agnostic "TME-Disruptor" Labels: Because CCR5 over-expression is a universal mechanism for solid tumor metastasis, CytoDyn's success in CRC without an ICI lays the groundwork for a tumor-agnostic label. They could market leronlimab as a universal adjuvant to be added to any standard chemotherapy backbone for aggressive solid tumors (breast, pancreatic, prostate) simply to amplify the base chemo's payload capacity."[/color]
All due respect, Ken. But on this particular point, I'm gonna say you are dead wrong. The CLOVER trial is settling once and for all that we don't need an ICI to prove our worth in cancer. And that is going to be... priceless.
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