Sek Kathiresan MD Profile picture
CEO @VerveTx $VERV; Imagine if a one-time treatment led to permanent lowering of LDL cholesterol: that’s what we are developing to treat heart attack

Apr 4, 2022, 6 tweets

Some patients with very high LDL-C who have already suffered a heart attack:

*may need both the PCSK9 and the ANGTPL3 pathways inactivated

*can we accomplish this with gene editing -

the switching off of two genes in the liver in the same individual?

#ACC22 @VerveTx $VERV

NHPs treated:
*day 0 with VERVE-101 targeting PCSK9 (one-time IV infusion)
*day 30 with ANGPTL3 base editor (one-time IV infusion)

*necropsy at day 90 -->
high level editing of each gene!!

69% editing PCSK9
61% editing ANGTPL3

Each edit designed to switch off respective gene

Day 0 - VERVE 101 Rx,
blood PCSK9 level plummets

Day 30 - ANGPTL3 base editor Rx,
blood ANGPTL3 level plummets

This will likely be durable for lifetime animal (person)!

With sequential dosing of our two products which are mRNA/guide RNA packaged in an lipid nanoparticle,

no sustained impact on LFTs

this is one of the key advantages of non-viral (LNP) delivery!!

Sequential dosing: no impact on total bilirubin

@VerveTx is advancing

a pipeline of single-course in vivo liver gene editing programs

to safely and durably lower LDL-C

and

treat atherosclerotic cardiovascular disease

#ACC22

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