snicobio

snicobio

06-07-2022

18:33

$ATXS Noteworthy data at EAACI 2022. Plasma kallikrein inhibition by STAR-0215 in cyno monkeys looks potent and durable. Argument can be made for improved efficacy over lanadelumab, but caveat: assay differences. Also, three 100 mg/kg doses before 84 day dose-free period.

Lanadelumab western blot assay in cyno monkeys at 25 and 50 mg/kg. Reduction of cleaved HMWK to ~35% d2 for highest dose of 50 mg/kg. Kaolin activation used instead of FXIIa.

Lanadelumab western blot assay (2.5 nM FXIIa) in health subjects. Reduction of cleaved HMWK from ~55% predose to ~25% d5 for highest dose of 3 mg/kg. Highest dose tested of 3 mg/kg (~180 mg total) is relatively low. Lanadelumab is approved for 300 mg q2w.

Lanadelumab western blot assay (2.5 nM FXIIa) in HAE patients. Reduction of cleaved HMWK from ~95% predose to ~35% d22 (around Cmax) for highest dose of 400 mg (two doses, d1 and d14).

When $ATXS goes clinical, it looks like they'll be using a higher concentration of FXIIa (10 nM) vs. the data above for lanadelumab (2.5 nM).

My takeaway is that these western blot/plasma activation assays are very sensitive. Lanadelumab is very potent when dosed properly (300 mg q2w), but doesn't get close to completely suppressing the generation of cleaved HMWK product following FXIIa activation ex-vivo.

Hopefully this helps those looking to interpret early clinical data coming from $ATXS's STAR-0215 in the next 6 months!



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