Editas Medicine, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Thanks for having us. Thank you.

It's great to be here.

Yeah. I'd be happy to. Editas Medicine is a company which is entirely focused on the development of in vivo delivered CRISPR edited medicines. Our philosophy centers around the creation of medicines that are highly differentiated for efficacy. That is that they will make a substantial and meaningful change to the standard of care. The second is that they exploit the unique properties of CRISPR editing. CRISPR editing can do many things, but there are certain things which are absolutely unique. Its ability to agonize or augment or increase the expression of potentially disease mitigating proteins as well as potentially repair them. I think the third thing is a focus on ideally disease areas where there are markers or biomarkers that became rapidly and easily accessed to allow rapid and meaningful, robust proof of concept in humans.

Finally, particularly with this in vivo focus, we want to be sure this very powerful technology is accessible and available, so that it can really have a significant impact on public health. That means a very deep dive into ensuring that we control the cost of goods and get it down. It's one of the reasons we don't actually do cell-based therapies at Editas anymore. This basically has resulted over the last four years when we first articulated that strategic plan and vision, to the manifestation of that strategy in our lead asset EDIT-401, which is a CRISPR edited medicine delivered by single IV infusion, that basically reduces LDL cholesterol, Lp(a), and ApoB by the mean of 90% in non-human primates. We are tracking to be in the clinic this year, with top line data next year.

Yeah. It is easy sometimes for us to forget, I don't know why, but because this is so common, that cardiovascular disease still remains the main cause of mortality and morbidity for humans on this planet. While we have made substantial progress over the years in managing cardiovascular death and cardiovascular complications, particularly around the control of blood pressure as well as cholesterol and LDL cholesterol, there is still a substantial proportion of patients who sit at very high risk for cardiovascular complications who cannot get their LDL cholesterol, which is the key bad cholesterol, down to a target level. That is notwithstanding statins and statins combined with PCSK9 inhibitors. Our approach is to essentially directly increase the synthesis of the LDL receptor in liver cells, and that receptor basically pulls LDL cholesterol out of the blood.

We have found a way by directly upregulating it that we can reduce LDL cholesterol in non-human primates by a mean of 90%. What does that mean in the context of non-human primate? Well, the non-human primate has been very successful in predicting biological effect sizes, both for cholesterol-lowering agents, as well as more recently for predicting the effect sizes of in vivo gene edited. That combination, we feel substantially de-risks that approach. There are a few other things that are relevant to how we have de-risked it, and if you do not mind, I might just go ahead and talk a bit about that.

Oh, yeah. Sure. The LDL receptor was a target that we identified again, through the application of our disease or therapeutic selection philosophy.

If you want to truly differentiate and change the standard of care, you cannot really go after pharmacologically validated targets because others have actually done that. We are actually using an approach where we leverage human databases and literature where gain of function or naturally occurring gain of function variants are identified in humans. In the case of LDLR, a gain of function variant in the LDLR was described a few years ago in an Icelandic kindred. In that Icelandic kindred, people who actually were heterozygous for this gain of function mutation had LDL cholesterols, which were ranged from about 13 milligrams per deciliter to about 60 milligrams per deciliter.

And then more recently, a French kindred has described a similar association, again with a similar gain of function variant. In both cases, this is a deletion in the three prime untranslated region of the LDLR gene, which results in the production of a messenger RNA transcript, which is stabilized and has a longer half-life because that deletion in the three prime UTR removes a number of microRNA binding sites. All that detail doesn't really matter. What really matters is that the message for the LDLR persists for longer, which means that more copies of the protein can be produced from that.

And certainly in our hands and in the lab, we have demonstrated that we're achieving at least a six-fold increase in LDLR expression in the liver of our non-human primates, and that is associated with the significant, and dare I say, unprecedented reduction in LDL cholesterol that we're seeing.