CSF huntingtin protein has been a bit less well characterized. What we do know is that in early stages of Huntington’s disease there’s no detectable mutant huntingtin protein in the CSF. It’s at levels that are so low that it’s not detected by the [indiscernible] use. However, over the course of time as neurodegeneration progresses, there’s a gradual increase in the level of mutant huntingtin protein in the CSF. So that tells us that it is in a way a marker of neurodegeneration. So if that is true and we believe it is and if that CFS protein is likely coming from killing from nerve cells when they become injured and die during the course of the process the ability to lower CSF huntingtin protein is an important marker that we are having a favorable effect on the brain cells such that they’re less injured, they are spilling less huntingtin protein into the CSF.
So all that is to say that’s what we understand about it. Quantifying what change is meaningful is a bit challenging. I don’t think anyone has an exact number other than to say obviously, if you have a marker of disease that is increasing over time as the disease worsens, if you could stabilize and ultimately lower that market that’s obviously very good. But I think the way we think about it is not in terms of any specific threshold but being able to look at our effects on the trajectory of CSF protein with a goal in mind. And we did share on the 12-week call that we are observing lowering in the dose cohorts at very early points in time before we know that we’re reaching steady state in terms of what we’ll ultimately be able to achieve in CSF protein lowering.
But we’re also going to look at that alongside other important markets such as NfL as well as the volumetric MRI and that together those will paint an important picture of the benefit that PTC518 will be able to provide for Huntington’s disease patients.
Unidentified Analyst: Got it. Very helpful. Thank you.
Operator: Thank you. And our next question comes from Tazeen Ahmad from Bank of America. Your line is now open.
Tazeen Ahmad: Hi. What would shift to a standard approval from the benefits you’re at now for EU practically change in terms of either commercial opportunity, reimbursement, or does that kind of not really matter in the grand scheme of things? And then as far as the cost savings that you mentioned about an annualized number of about $150 million or so to clarify upon what you might have said before, could there be room for additional cost savings beyond what you just described as we get closer to 2024 and you take a closer look at your portfolio? Thanks.
Matthew Klein: Great. Thank you very much for the question, Tazeen. On the first question regarding the conversion from a regulatory standpoint I think the impact is perhaps you don’t have to go through a process every year of getting the renewal. But more importantly and to the point of your question, the commercial type I’ll let Kylie talk more about that.
Kylie O’Keefe: Yes. So Tazeen in answer to your question around the benefit, I think what the team has done is a remarkable job of securing very favorable pricing and market access with conditional approval. And not only being able to secure it but maintain a really favorable pricing corridor over the years of maturation of the product, which is not easy to do. I think from a benefit perspective we don’t see a huge upside when it comes to the countries that we’re already launched in with pricing and market access. There are some smaller countries that would open the door to a discussion post conversion. But I think where the true upside is the countries that we don’t have registration in yet.
