Intellia Therapeutics, Inc Morgan Stanley 24th Annual Global Healthcare Conference

Sure, and thanks for the question, and happy to be here. We've pioneered the in vivo gene editing space. In the early days, as CRISPR was coming to be, I think a lot of people went off into ex vivo and started off in that space. We bit the bullet and went directly to the in vivo editing space, where that's where most of the actual targets reside in the body. The challenge there is solving for delivery, right? We benefited from people who'd gone before us in terms of delivering RNA, and set off with a lipid nanoparticle platform that we developed. We showed that you can open up the liver, which is, here we are, end of phase III for the BLA for our first indication, HAE, and then well into a phase III trial for TTR cardiomyopathy and polyneuropathy.

I think what the opportunities, still there are several that reside in the liver, but developing targeted LNPs to get outside of the liver to certain spaces, and then finding other therapeutic delivery modalities that take you into the brain and the lung, that lies ahead. I think as those insights come, there'll be many, many very valuable targets to pursue. At this point, we're really most interested in getting the first ones across the finish line and showing that we can successfully commercialize a CRISPR-based therapy.

Well, we heard from the FDA just a week ago that they've accepted the BLA, which is wonderful news. We had benefited along the way from our RMAT designation and other work that we had done with pilot programs and CMC. As you know, many of the RMAT-designated programs then benefit from a priority review, which we know that we'll have. We ultimately got a PDUFA date now of March 10th. One of the things we were obviously wondering about, given that we're the first example, was whether or not there'd be a need for an advisory committee, but the FDA has said that that's not something that they're currently planning on doing. We'd, at this point, I think, be surprised if that were to come. So from a confidence level, we think we've got a very, very strong package. The data are there for anyone to see.

The compound has just excellent efficacy and a very, very clean safety profile. So we look forward to the questions, and that's what lies between now and March 10th.

Yeah. We tried to develop the program as essentially an all-comers program minus the pediatric patient population below age 16. There were no restrictions based on prior therapy, type of therapy, degree of disease, that kind of thing. In fact, the patient population that ultimately came into the phase III program largely represents what is the market in the U.S., 70% LTP, 30% on-demand therapy, patients with varying degrees of control, and importantly, 20% of the patients in that phase III trial with complete control. We think that the product has broad appeal, and we would expect that the label will reflect that.

I am going to turn to Ed to speak to the market piece.

Yep. Yeah, I will talk to that.

Maybe we will start with the clinical data, since that is the basis of a lot of these conversations. We have all been trained to talk about attack rate reduction. We had 87%. That is sort of table stakes for today's LTP market, as we like to refer to it. But as importantly is the data that we have in terms of how many patients have an attack-free state at the 28-week primary observation period. In our case, that also is accompanied by no therapy, by definition. So we had 62% attack-free status. In both cases, that is as good or better than anything that has been reported. I would like to extend that, though, because I think there are two other bits of information as we think about the opportunity ahead that we are really excited about.

If you take a big step back and you look at all patients we've treated, phase I, phase II, phase III, that's in excess of 100 patients. All patients eventually get to an HAE-free state. I'll just say it again, every single patient has gotten to HAE-free, and none have gone back to HAE. As you think about healthcare resource utilization, that's an important consideration. It is already a very expensive disease to treat. The reason being is, for the most part, that HAE therapy, which can be in excess of $700,000 annually. When we show up to a payer conversation, it's very interesting because their question is, "Well, what is the right multiple to think about?" Right? We will test things like 2, 3, 4, 5 times multiple. Not surprisingly, when you get to the upper end, you're going to face a lot of resistance.