This work was led by the BlueSky-less Fred Tremblay. Fred’s scientific rigor and unflappable leadership style truly drove this program. Congratulations mon ami to you and the entire team!
9/9

Our preclinical data strongly supports the promise of epigenetic editing as a potential ‘one-and-done’ approach for the treatment of hypercholesterolemia, and more generally as a therapeutic approach to silencing loci without cutting, nicking, or changing the DNA sequence
8/9

Our human PCSK9-targeting epigenetic editor is fully cross-reactive against cyno PCSK9, & we demonstrated that a single administration led to rapid and sustained, 90% reduction of PCSK9 protein, resulting in a clinically meaningful 70% reduction in LDL-C in non-human primates
7/9

Not only was this methylation-driven silencing durable in a homeostatic liver, but both silencing and methylation were fully maintained during liver regeneration, indicating durability through cell division in vivo!
6/9

We confirmed that mRNA/gRNA encoding our human PCSK9-targeting epigenetic editor packaged into an LNP was able to reduce circulating PCSK9 protein 98% for a year after a SINGLE ADMINISTRATION in a human PCSK9 transgenic mouse!
5/9

We designed an mRNA-based #epigeneticeditor: DNA-binding domain fused to a DNA methyl-transferase domain & a transcriptional repressor domain which, together w/ human PCSK9-targeted gRNA, deeply & specifically methylated & silenced PCSK9 in primary human hepatocytes in vitro
4/9

One of the first programs we launched sought to develop a potent, transiently expressed epigenetic editor to durably silence #PCSK9, a genetically and pharmacologically validated target that regulates plasma LDL-C, a causal factor for heart disease
3/9

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