Editas Medicine, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Yeah. So thanks very much, first, Eric. Great to be here. Where the company is today is Editas Medicine really has completed its focus on being an in vivo therapeutics company that uses and leverages CRISPR editing to create therapeutics. Philosophically and operationally, we're aligned in that we choose to develop medicines that really transform the standard of care. They have to make a meaningful change, and that's efficacy-driven change to the standard of care. Secondly, they have to be mechanistically differentiated. We leverage the unique capabilities of CRISPR editing, and what that means is that we don't use it to do things that other modalities can do. A very good example is that we really focus on creating gain-of-function edits that basically increase the levels of disease-mitigating proteins.

Third, we are very careful in choosing the diseases that we will actually bring those medicines into, in that we will focus on diseases in which there is a biomarker that we can readily measure and lead to rapid decision-making around dose selection. Then finally, and this is an important part of the pivot that we've completed being a fully baked in vivo company, is that we're very much focused on creating easy-to-use, single infusion or injection, low cost of goods, durable medicines that can be accessible to patients that need them. And that philosophy is epitomized in our lead program, EDIT-401, which essentially is differentiated or has the potential to be differentiated in efficacy by achieving a 90% reduction in LDL cholesterol, as we've demonstrated across non-human primates, along with other atherogenic lipoproteins, including Lp(a) and ApoB.

It is simple to use, requiring a single infusion, and it generates the effect by creating or mimicking a gain-of-function variant that increases levels of LDLR, which exceed those that have been seen with other approaches.

Well, we will have accomplished a number of things that we can stage over the next 12 months. The first is that we will dose patients this year, and we are tracking well for that, having submitted documentation to the HREC in Australia and being in dialogue with them. We continue to stay on schedule for dosing this year. In the first quarter of next year, we will share safety data from the first cohort patients. Then later in 2027, we will share top-line data that includes safety and efficacy across multiple dose cohorts.

I think tools are very important, but how you use the tool is also important. Our key technology, using CRISPR-Cas9 and CRISPR-Cas12, essentially has the potential to create edits or even deletions. We leverage that in a way, I was saying earlier, that is unique to gene editing. One of the things that you cannot really do very well with a monoclonal antibody, an antisense, or an siRNA, with certain very rare exceptions, is increase the levels of protein. We are actually using our editing technology, or indel technology, to essentially create or mimic naturally occurring gain-of-function variants that increase levels of protein. That really is at the core of our philosophy, is how we use the tool.

We've already identified, and really, I would say at the beginning of that journey, several gain-of-function potential targets. We have disclosed two of those. One is our EDIT-401, which we'll discuss later, and the other is our in vivo HSC-targeting therapy with the potential for sickle cell and thalassemia, which we have kept in discovery because of our entire focus of bandwidth and resource to advancing 401. But we continue to optimize that, and as I said, we have several other targets. Then actually, we continue to explore and search for additional gain-of-function variants. But the truth is, we expect to find others.

Well, I think there are probably several reasons. In many ways, they had enough to pioneer. I think our peers have done a really magnificent job of pioneering in vivo editing. Kudos to Intellia for betting on LNPs before COVID. I don't know if you remember, before the pandemic, LNPs had not been validated across billions of human beings. So they did all that pioneering work and are highly committed to indel, and the same for other therapeutics companies. We did the pivot a little later, and it gave us an opportunity to sit back and say, "Okay, how do we differentiate, or what additional things can we contribute to the field?" I think this idea of leveraging an indel tool to focus on a gain-of-function was a clear area that we could actually really contribute and expand into.