Unidentified analyst: Hi. This is Jack on for Annabel. Thanks for taking my question. So for the Subretinal formulation of 314 in wet AMD, what’s the right amount of follow-up time that FDA is looking for to establish safety and durability there? And what might the value proposition be here for the payers when you think of pricing this, considering that many of these patients are elderly and may not see the maximal benefit of a long-term treatment?
Ken Mills: Steve, do you want to take the regulatory part here?
Steve Pakola: Sure. Hi Jack. Yes. So, taking the first part of your question, the duration from a regulatory standpoint as far as follow-up. We’ve gotten very clear feedback back as far as the end of Phase 2 meeting that allowed us to finalize the pivotal program that really is a class requirement having one-year safety and efficacy data, which also was somewhat informed by efficacy, but predominantly by gene therapy aspect. We’ll also have longer term follow-up data from a lot of the patients from our pretty sizable safety database. And we actually already have from our Phase 1/2 data base out through four years, good safety and also good durability from an efficacy standpoint. So, I think both based on other programs, even outside the eye that have shown durability out even beyond a dozen years, for example, in hemophilia with the same AAV serotype AAV8.
And then now our own data gives us a lot of confidence on duration of efficacy. And I think that’s obviously going to inform the value proposition, having durable efficacy evidence. And the value proposition importantly is more than just decreasing treatment burden and visit burden. Really, the big unmet need here is by breaking the barrier of the treatment burden, it ensures that these patients aren’t going to have the ongoing sustained anti-VEGF activity that they need to prevent vision-threatening complications that they simply aren’t getting now both in terms of wet AMD and diabetic retinopathy because of the treatment burden. So, there’s various layers of the value proposition, treatment burden, visit burden, and actual vision and complication outcomes.
Ken Mills: Yes. And I would add, Jack, that I think it’s pretty well-established by a lot of different sources that the cost of the cost related to blindness that’s associated with wet AMD is on an annual basis, something that can be in excess of $100,000 a year and that’s separated from the cost of drug. So, when we think about a wet AMD patient, you’re talking about the life expectancy might be on the order of 10 to 15 years. I think in the real world, there’s a need there for recovering the vision that is being lost because people aren’t staying compliant with the existing treatments and the cost and the — obviously, the effect that that’s having on a productivity basis with respect to the effect that it has on the families of those patients as well, is significant.
And so durability is everything. I like how Steve brought up the four-year evidence, which just continues to grow. It’s there as a backstop for things on a regulatory basis, but I think also important in the commercial setting.
Unidentified analyst: Great. Thanks so much.
Operator: Our next question comes from the line of Mani Foroohar with Leerink Partners.
Mani Foroohar: Hey, guys. Thanks for taking the question. Obviously, you have fund decisions to make, but obviously the right thing to do. You’ve outlined the press release a little bit of detail around about $100 million of savings, et cetera, couple of years. Could you give us a sense of where that tempo is? Like should we expect that to drop in immediately starting in 1Q and be fairly linear on a quarterly basis? Or is it something that’s a little more front loaded, a little more backward over the first couple of years? And beyond that, how should we think about post that two-year period, what is the implication on OpEx longer term?
