I misread that that was the PDFF number. It was 27

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I misread that that was the PDFF number. It was 27.64 in haplotype group the same as no n- haplotype. Although you'd still expect an increase.

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That's about as clear to me as mud.

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So ask yourself why there was no breakout of cT1 levels in 700mg. Could it be because there were few with >950ms? With higher CCR5 expression higher ms may have only been in the haplotype group. Wouldn't you think that would affect the numbers between haplotype and non-haplotype.

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I believe any patient in the 700mg group who was not a part of the 700mg HM group had NORMAL quantities of CCR5 receptors, otherwise they would have been included in the HM group. Along those lines, I do not believe any HM patients were a part of the Placebo group. I do not believe there were any HM patients in the 350mg group either. Part of my reasoning for this comes from CR in last conference call 6/30/22:

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There are genetic differences in CCR5 that have been studied as related to the risk for HIV and HIV progression and some CCR5 haplotypes over produced CCR5 thus increasing the risk for HIV b/c there is more CCR5 that the virus can use to enter. Since these patients have increased CCR5, from these HIV studies, we have hypothesized that t hey may need more LRM in the NASH study. (Explaining why they gave 700mg to the HM group.)
The exploratory analysis showed a 28% reduction in MRI PDFF fat, with corresponding reduction in MRI cT1 fibro-inflammation for patients with over expressed CCR5 haplotypes, when treated with 700 mg of LRM. and the number of patients were small, (5) representing only 23% of those in the 700mg group, but we noticed key distinct changes in biomarkers for this haplotype group, perhaps suggestive that these CCR5 haplotype patients may have a different etiology for NASH. But further exploratory studies need to be performed.

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The difference in PDFF in all 350 mg was 15.79%. The difference in PDFF for the total 700mg group was only 6.1%. White fat to Brown fat transposition is correlated to CCR5 expression and thus blockade. A novel idea but do you think it's possible that the 700mg group outside of the haplotypes had less severe NASH. Which means less CCR5 expression. Which means lower cytokine expression. Which means less fat and less scarring. Which means you will see a lesser change and lower percentages.

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Yes, I think it is quite probably the case that the 700mg normals had less severe case of NASH and were in majority NAFLD.
That does NOT mean less CCR5 expression at all. Where are you getting this from? Yes, it is less than the HM group, but they are few and far between. They have a genetic mutation.
Lower cytokine expression? No. CCR5 expression is NORMAL in this group. These are not Long Hauler Patients.
Less fat? No - Maybe. Less Scarring? Yes, probably.
Lesser change? Had they been treated with 350mg instead, we may have realized similar results or Better results. But worse results would not have been found.

Please refer to my recent post:
https://investorshangout.com/post/view?id=6432233

350 would have found increased Intracellular Adhesion Molecule thereby indicating increased Metabolism of Fibrosis.
700 showed reduced Intracellular Adhesion Molecule despite increased dosing, completely consuming all the CCR5 receptors, the systems became "torn" between entering the metabolism of fibrosis vs.the macrophage attack of the dying hepatocytes. At 350mg, it was enough to persuade the system to enter and remain in the metabolism of fibrosis while at 700mg, the system was "torn" or divided into some metabolism of fibrosis and some macrophage attack of the dying hepatocytes, with the fight being won by the macrophage attack of the dying hepatocytes.

By lowering the dose to 350, the 700 mg normal patients may have faired modestly better because their systems would not have been split into two diametrically opposed polar opposite directions, but would have entered and remained in the metabolism of fibrosis mode until it reached such low levels that it would then enter back into the macrophage attack of the dying hepatocytes, because then, the patients would more definitively be back in the NAFLD stage and not NASH.

If 350mg were used instead of 700 mg in the normal group, TNF would have been reduced in that 700mg group like it was in the 350mg group. A reduction in TNF verified that the treatment was effective in reducing both fibrosis as well as steatosis. This was evidenced in 350 and 700 HM, but the opposite occurred in 700 normal.

Had those 700mg normal patients received 350mg instead, Interferon Gamma would have decreased instead of increased. That would have proved that these patients would have lost fibrous tissue. Instead, with Interferon Gamma increased, the macrophages were attacking dying hepatocytes more than they were metabolizing fibrous tissue.

Had the 700mg normal patients been treated with 350mg instead, the IL-4 would have increased as it did for the majority of the 350mg instead of decreasing like it did for those 700mg normal. That would have proved that they would have entered the metabolism of fibrous tissue, rather than be more heavily weighted towards the macrophage attack of the dying hepatocytes.

Had the 700mg normal been treated with 350mg instead: VEGF would have been reduced and not increased. VEGF produces Nitric Oxide which is classic for the macrophages being in the macrophage attack of the dying hepatocytes mode. VEGF goes down when the system is in the metabolism of fibrosis mode which happened in the 350mg group.

I tried to develop a modest understanding prior to the conference here:
https://www.reddit.com/r/LeronLimab_Times/com...onference/
Just take into account, that I wrote that before looking into the biomarkers as far as I did since then.

This was taken from there:

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Since we know that for serious disease, the potential for LRM to make more of an effectual change is greater. It may have been that the 700 normal group were healthier than the 700 HM, the 350 (who were all but one greater than 875 cT1 baseline) and the Placebo groups? If that were the case, it would explain why the 700 normal group did not benefit with LRM administration because they may already have been somewhat healthy.

We know that the 350mg group was 22 patients. We know that the 700 HM group was 5 patients, and these are typically sicker because their CCR5 receptors being in higher quantity function worse. We know that the Placebo group was 28 patients. All together that is 55 patients, leaving 17 as 700 normal patients. 17/72 is 23.6%. 55/72 is 76.3%. The study says that 58% had baseline of > 875 cT1. 58% of 72 is 42 patients had baseline > 875. We know that 21 of the 350 had baseline > 875 cT1. We can assume all 5 700 HM had baseline > 875 cT1. Together that is 26 leaving 16 . Let's say 10 Placebo had baseline > 875 leaving 6 700 normal patients with baseline > 875. That would mean 16 of the 700 normal patients had baseline < 875 or mild disease. 16/22 is 73%. Possibly 73% of 700 group had mild disease which may be why 700 normal were not benefited by LRM administration.

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Lastly, I wrote there:

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For Fibrosis, the 350mg >950 cT1 performed the best, while the 700 HM performed 2nd best, and the 700 mg performed better than Placebo. 700 did better than Placebo even with mild disease, and did very well in the HM group where CCR5 was over expressed on surfaces of HSCs, but not quite as good as in the 350 >950 cT1 group who had the worst disease. When the baseline disease is worse, the benefits of LRM treatment are greater. Regarding Fibrosis, it appears LRM is modestly effective in reducing rate of fibrosis and scar tissue development even while given in mild disease.

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