What if it's not all about receptor occupancy?
Post# of 146077
Leronlimab has been studied primarily in HIV, cancer, and patients in the hospital with serious covid. All of these indications are life-threatening, and I would venture a guess that you'd want to have complete receptor occupancy in these indications. (!) But in chronic conditions perhaps partial receptor occupancy is clinically meaningful, as the results of the NASH study seem to suggest.
We are still early in the game with respect to Leronlimab and it's effect on the human body. The data set from the NASH study monitored an impressive number of variables--80 as noted on the heatmap--and we haven't seen this kind of granular data before. Of course the heatmap is an imperfect representation of said data, and we will need to see the numbers in a scientific journal. And of course, in the fall we will have results from the mouse study, and as Ohm suggests, we should have a pretty good indication of whether or not the NASH study included enough Northern European participants with the delta 32 mutation to skew the results to favor the 350mg cohort. Which, of course, would invalidate this whole train of thought, and leave me eating crow!
But if this data holds up it's kind of a whole new ballgame... It would suggest the era of immune modulation is at hand, with leronlimab leading the way. I hope these results are confirmed in other studies--if so, we are going to be wealthier for it! And healers will have a very important therapeutic in their arsenal.
A couple further comments from the heatmap. The placebo arm is pretty neutral, as you might expect. But the leronlimab arms of the study--whether 350 or 700mg--tend to light up with color. This suggests to me that the drug is unusually active across a broad range of the factors studied--especially the factors grouped together as "Serum Pro-Inflammatory Assessment." (These include such factors as Macrophage Inflammatory Protein 1A, Tissue Inhibitor of Metalloproteinases 1, TNF Receptor 2, Vascular Cell Adhesion Molecule 1, Interferon Gamma, Brain-Derived Neurotrophic Factor, Plasminogin Activator Inhibitor 1, IL-10, IL-3... etc, etc).
The second thing is based on a comment in the paper that ""CCR5 haplotype analysis is suggestive that specific haplotypes may be better suited for the 700mg dose of leronlimab." They identified a small number of these patients in the study, and boy did they respond well to the larger dose. The authors used red for increases, and green for decreases, and so the 700mg haplotype column literally lights up like a Christmas tree! While I confess I don't know what a haplotype is, apparently Cytodyn can test for and identify as prospective patients. So they are finding more and more information about dosage and who responds, which they can actionably use in trial design as well as in the clinic (eventually).
So--the NASH study obviously left a lot of questions out there, perhaps more than they answered. But if you take the data at face value, we have a lot to be excited about. Following Occam's Razor, perhaps the simplest explanation--the data is sound--is correct. Saying 350mg out-performs 700mg in parameters that haven't been studied before doesn't defy logic, it simply fills the gaps and expands our knowledge of this brave new molecule. And gives a tantalizing hint of it's potential in chronic, rather than acute, conditions.
Well, I think Dr Jay is moving forward on the basic science in an appropriate, measured way. And he's going to do a colon-cancer study that if successful will set us on a short path to FDA approval. So I think it's great to see movement forward on both fronts. It's frustrating to continue to be patient, but it's all part of the process. And we can continue to pick up shares while they are so cheap! (Not for long though, I would guess).
To borrow a tagline... Shall see!
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