Pegozafermin and Leronlimab look to have very diff

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Pegozafermin and Leronlimab look to have very different mechanisms of action. They might produce a synergistic effect if trialed together.

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A combo study was done with an FGF21 agonist (Pegozafermin's mechanism of action) and Cencriviroc (CCR2/CCR5 blocker). The combination did do better than either alone. However results might not be the same if leronlimab is used. Cencriviroc preferentially binds to CCR2 and weakly binds to CCR5. CCR2 also has a low expression compared to CCR5. Most importantly CCL5 (RANTES) does not bind to CCR2. With weak binding to CCR5, lower expression of CCR2 and no binding of the ubiquitous CCL5, Cencriviroc would be less effective.

A combo with leronlimab may show an improvement or may be similar to leronlimab alone. The downstream effects of leronlimab and FGF21 upregulation have similarities.

Combined Therapy with a CCR2/CCR5 Antagonist and FGF21 Analogue Synergizes in Ameliorating Steatohepatitis and Fibrosis