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This is nothing really, but its interesting that 350mg reduces inflammation in NASH and 700mg has immune implications.

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700mg in NASH reduces inflammation quite well as seen by the results in cT1 and which would be indicated by PDFF. Yet in biomarkers it shows worse results than placebo. PDFF and cT1 scans would be done in the hospitals. Biomarker testing would have been done by whomever Amarex used. I trust the hospitals to have done them correctly, not so with Amarex's choice.

Dr. Recknor deduced that the greater immune boosting effects of leronlimab at 700mg were due to leronlimab double occupying the CCR5 receptor, the change in conformity inducing those effects. Unlikely, leronlimab was engineered to bind to very specific sites and would block other binding. The difference in immune activation can be easily explained by the difference in receptor occupancy between 350mg and 700mg. The higher occupancy would result in greater effect.

I ran across a paper a couple of days ago while looking at gp120. It goes into depth on CCR5 binding. I suspected that the N terminus would be the focal point of leronlimab blocking other ligands. That does seem to be the case.

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Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist

On the basis of their N-terminal sequence, we expect that other identified CCR5 agonist or antagonist chemokines feature respective similar deeper (6P4[CCL5]-active-like) or less deep (5P7[CCL5]-inactive-like) positions of their N-terminal turns within CRS2.

The CCR5 chemokine agonist ligands CCL3 and CCL4 are closely related to CCL5 having similar N-terminal sequence lengths and compositions. We therefore expect that these chemokines also adopt the straight-hinge conformation and use the same activation mechanism as [6P4]CCL5

It is interesting to observe that many chemokines undergo posttranslational proteolytic processing leading to different N-terminal lengths, which may constitute a layer of regulation Thus, a CCL5 variant lacking the first two N-terminal residues (CCL53–68) behaves as a natural chemotaxis inhibitor, and a 10-fold higher concentration compared to wild-type CCL5 is required to induce a significant calcium response (37). Similarly, CCL54–68 has an about 10-fold lower affinity for CCR5 compared to CCL53–68 or wild-type CCL5 and is less potent in stimulating lymphocyte chemotaxis or inhibiting HIV infection. These findings are in complete agreement with the lack of contacts at the bottom of the CCR5 CRS2 region expected for such CCL5 truncations.

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The activating force exerted by the deep binding [6P4]CCL5 N terminus appears to be stabilized by a cluster of hydrophobic CCR5 residues in TM2 and TM3 that line the extended N-terminal hinge of this agonist chemokine. Understanding this force balance may help in the design of small-molecule agonists, which could activate the connector region at the bottom of CRS2 by pushing against this counter bearing.
https://www.science.org/doi/10.1126/sciadv.abg8685

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If the purpose is to disable CCR5 then no need to design anything, leronlimab is already here.