twinter, you have now officially extended the leronlimab thesis into cardiology, neurology, gastroenterology, and oncology across four separate disease verticals in a single comment thread. At some point the question stops being what leronlimab does and starts being what CCR5 is actually for in the first place. The answer, increasingly, appears to be: a lot, ie: ohm's list.
On the cardiac risk-benefit question in mCRC patients: you are right that most refractory mCRC patients carry underlying cardiovascular comorbidity. The honest answer is that the net vascular effect of CCR5 blockade in that population is genuinely complex given the dual Treg and CD8+ homing roles discussed in the prior exchange.
But here is the practical framing: the CLOVER backbone does not include an ICI. The vascular shield argument is most acute in ICI co-administration settings where reinvigorated CD8+ T cells are being systemically activated and need somewhere to go. In the TAS-102 plus bevacizumab backbone, the activated CD8+ compartment is not being pharmacologically amplified the way it is under pembrolizumab. So the cardioprotective benefit of CCR5 blockade in CLOVER patients is probably modest, and the Treg homing disruption nuance matters proportionally less. The big cardiac story is the ICI combination setting, exactly where you landed, so I suggest CytoDyn incorporate some cardiac biomarkers and/or imaging pre & post treatment and then a strong retroactive study may be compiled to make the argument to include leronlimab for any person on an ICI, to have leronlimab coadministered. That would be massive. Think of all the statins prescribed.
On first-line TNBC and the tumor fighting back quickly: that framing is exactly right and it maps onto the pre-PD-L1-upregulation window discussed earlier in this thread. Hit a tumor with leronlimab before it has built its full suppressive architecture, before the CCR5-mediated myeloid wall is established, before the CD8+ T cells have been routed into the exhaustion pipeline, and the immune system gets access to a target it has never been able to reach cleanly. The tumor's adaptive response, upregulating PD-L1 and alternative checkpoints, tells you the immune pressure is working. That is not a sign of failure. That is the tumor showing you where the next gate is.
First-line anything with leronlimab is a different biological conversation than salvage-line leronlimab. Thank you plotinus for https://investorshangout.com/post/view?id=6834285 . Spot on. The architecture being disrupted is younger, less entrenched, and proportionally more vulnerable. The data from that setting, whenever it arrives, is going to be a different register entirely from what CLOVER is measuring in a heavily pretreated population.
The big medical AI program you already imagine exists. It is called the Natera database, it has two million plasma timepoints, and it is currently pointed directly at the CLOVER population. Given the CytoDyn + Natera partnership, we will know what to map into.
Close enough for now.
On the cardiac risk-benefit question in mCRC patients: you are right that most refractory mCRC patients carry underlying cardiovascular comorbidity. The honest answer is that the net vascular effect of CCR5 blockade in that population is genuinely complex given the dual Treg and CD8+ homing roles discussed in the prior exchange.
But here is the practical framing: the CLOVER backbone does not include an ICI. The vascular shield argument is most acute in ICI co-administration settings where reinvigorated CD8+ T cells are being systemically activated and need somewhere to go. In the TAS-102 plus bevacizumab backbone, the activated CD8+ compartment is not being pharmacologically amplified the way it is under pembrolizumab. So the cardioprotective benefit of CCR5 blockade in CLOVER patients is probably modest, and the Treg homing disruption nuance matters proportionally less. The big cardiac story is the ICI combination setting, exactly where you landed, so I suggest CytoDyn incorporate some cardiac biomarkers and/or imaging pre & post treatment and then a strong retroactive study may be compiled to make the argument to include leronlimab for any person on an ICI, to have leronlimab coadministered. That would be massive. Think of all the statins prescribed.
On first-line TNBC and the tumor fighting back quickly: that framing is exactly right and it maps onto the pre-PD-L1-upregulation window discussed earlier in this thread. Hit a tumor with leronlimab before it has built its full suppressive architecture, before the CCR5-mediated myeloid wall is established, before the CD8+ T cells have been routed into the exhaustion pipeline, and the immune system gets access to a target it has never been able to reach cleanly. The tumor's adaptive response, upregulating PD-L1 and alternative checkpoints, tells you the immune pressure is working. That is not a sign of failure. That is the tumor showing you where the next gate is.
First-line anything with leronlimab is a different biological conversation than salvage-line leronlimab. Thank you plotinus for https://investorshangout.com/post/view?id=6834285 . Spot on. The architecture being disrupted is younger, less entrenched, and proportionally more vulnerable. The data from that setting, whenever it arrives, is going to be a different register entirely from what CLOVER is measuring in a heavily pretreated population.
The big medical AI program you already imagine exists. It is called the Natera database, it has two million plasma timepoints, and it is currently pointed directly at the CLOVER population. Given the CytoDyn + Natera partnership, we will know what to map into.
Close enough for now.
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