Jan Mikkelsen: Thanks for the question. Let me start with your last question about the annualized high velocity. We always have known that growth hormone had a positive effect on achondroplasia. Sometime it has been a little bit unclear what has been the magnitude on that because it typically have been small trials. When we saw the trial coming out from the Japanese group, pretty well controlled, falling patient up to five-years, the number is nice, 41. Everything looks great. They have one year before treatment follow on what is the annualized high velocity before treatment and it is about 4.2 exactly what you will expect to see out from this kind of demographic. And the first year, annualized high velocity up on 7.3, 7.4. That is more than I’ve seen any kind of CMP treatment ever give it.
And when you have 41 patient, I always feel that it is a number that gives me some pretty good comfort. And it is the best analyzed high velocity I have ever seen in any hype trial with achondroplasia patients. We went back and analyzed 20 publications about all small trials, some of them all of them. And if we have been smart, really have gone to the literature in-depth, then we could actually have seen it because often these 20 publications, we nearly got the same number when we added everyone out. So this is not surprising. It is something that has been in the literature, have potentially been understated, undervalued. But there is no doubt, best Analyze high velocity you can get in that contemplated today is on growth hormone. The problem with that is we could really address co-morbidities, I don’t believe that.
I believe that the biology behind the achondroplasia is a much more complicated by logical impact on the hyperactive FDR to U.S. Sector. And there it comes in because in the end, we are just starting the beginning of the beginning of achondroplasia treatment. We are not in the end of the beginning even. We are in the beginning of the beginning because we need to address the comorbidities. So this is why we believe the treatment is potentially moving to a combination treatment. Well, CMP will address some of the biological systems where we believe achondroplasia, the hyperactive FDL3 pathway are modifying and disease that basic are also of muscle impact. And you asked me why did we see that? It was basically the patients, the parents, the caregivers that came back to us.
We got in the patient reported outcome. We can see after one or two months that suddenly say that patient providing much better, function much better and we said it cannot be growth. And then we started to analyze this and we realized that is a strong muscle component of that. And what we would like to do when we have our CMP update, we will give you the biology behind it, explain why we do that. And also, we believe that it is important for us also to provide you with data with the combination therapy, because I believe in the combination therapy, you can get whatever analyzed high velocity potentially the same as you can see in growth hormone deficient up to 10, 12 centimeters.
Operator: The next question comes from Yaron Werber with TD Cowen.
Yaron Werber: Maybe one very quick one and the second one is a little bit bigger. Just on the PTH, the refiling is going to be sort of in the next week or so. Can you just comment, did you sort of by this point work out all the analysis that FDA is going to want you to do? Or do you feel like you have good clarity? And then secondly, on the preclinical GLP-1, if the data with some obviously looks interesting on a monthly basis. What are sort of the next steps as you see them before you can start IV enabling study? Is it you are still trying to fine tune the construct? Or is it potentially trying to figure out, is this something you want to take yourself? Or is it something that you want to ultimately potentially partner?
Timothy Lee: This is Tim. Let me take the first part. As Jan on his prepared remarks, and besides the information that we just discussed, we are not going to provide, we are not going to comment further on the resubmission process.
