Sean Nolan: Yes, so for this protocol, all patients who are over the age of 18 will be started on prednisolone, 1 milligram per kilogram from day minus seven. And that will be continued out to 16 weeks and then it’ll be tapered off over a certain number of weeks down to 0.5 milligrams a kilogram and then 0.25. These patients also get sirolimus at a much lower dose than what’s used for transplant based on the body surface area. Also starting around day minus seven and runs, if I recall, 36 weeks and then it’s tapered after that. We’ve looked extensively into the literature, we’ve talked to all the experts who treat Rett syndrome and they’ve all said that both prednisone and sirolimus no way or form impacts the clinical progression of the disease. Some people have actually done some experiments too, and they say there is no impact and therefore any improvement seen with the disease is actually due to the gene therapy that has been given.
Jack Allen: And then just as it relates to the sirolimus dosing and the potential implications that had on the seizures the patient two, have you given any consideration to modifying that dosing moving forward?
Sukumar Nagendran: Yes, we’ve actually have started looking into it, but the issue is sirolimus with prednisolone and we have some experience now with the GAN program where we showed that patients could be dosed regardless of the seropositivity to AAV9 antibodies, which is actually very helpful, especially given that our gene therapy is working in adult patients as well, where there is a higher seropositivity. But we have to balance that, as you said, with the type of anti-seizure medicine being used, especially if levels do drop significantly like what happened with Dilantin. So I guess the bigger question is, if — are there other medicines that we can try, which are not processed in a way through the liver and impacted negatively by sirolimus. So I think that’s something that we have to continue to assess for now.
Sean Nolan: Yes, I would just add to that, Jack, that it was patient one that was on the Dilantin. And the other thing, at least based on her history, is she’s tried multiple products to control the seizures, and Dilantin was the only one that appeared to work. So, it may be a bit of a unique circumstance. We’ll just have to see and monitor carefully as we proceed in the study.
Operator: Thank you. The next question comes from Joon Lee from Truist Securities. Please proceed with your question.
Unidentified Analyst: Congrats on the data and thanks for taking our question. This is Mandy for Joon. So you have a closed direct competitor in gene therapy or Rett syndrome from Neurogen NGN-401. Could you please elaborate on anything specifics in your program that could be viewed as a strong differentiator of your program? I mean from construct, design, route of administration those levels because the capsid seems to be the same. And I have a second question, which is related to TSHA-120 in GAN. So are there — what’s the latest there? Is there any takers or are there any negotiations going on for this program? Thank you.
Sean Nolan: Thanks, Joon. Well let’s, let’s start with the GAN question. I would just say there’s not a lot to comment on specifically. We are in the process that we’ve outlined of stepping through strategic alternatives, and I wouldn’t want to comment on anything until it’s actually been resolved. So stay tuned on that one, but nothing to report specifically. As it relates to Neurogen, I guess a couple things I could say high level would be — you’re correct that both constructs use AAV9 as the capsid. But that’s where the similarities end. So number one, we have a mini gene. They have a full-length gene. Promoters are slightly different. I think that a key aspect is really the regulatory element, miRARE that we have versus the exact technology that they have.
So, the way I would describe our construct is that, it’s able to take into account and read the endogenous levels of MECP2 in each cell that it goes into. And based on the level of endogenous MECP2, it will either create exogenous MECP2 or not. And so I think that’s the distinguishing feature where our understanding of the exact technology is that essentially regulates itself. It is not taking into account the endogenous levels of MECP2. So potentially, there could be additional risk for over expression with that construct. I mean, we’ll find out in the clinical setting. But that’s a key area of differentiation. I would also just note that we’re going through intrathecal delivery versus the ICV route that the Neurogen team is embarking upon there.
So, there’s a lot of differences. I can’t comment anymore on the Neurogen program. I’m not aware of anything specific. But I would just say at this particular point in time, we’re quite pleased with what we’re seeing in our construct. And I would just go back to the first question that Whitney asked. And proof of concept with our construct with these two very different phenotypes and genotypes is encouraging, right? We saw a very severe patient that would arguably have very low levels of MECP2, and we’re seeing a nice response. And in a patient with a less severe mutation, where you would expect her to be producing significantly more MECP2, we’re seeing response coupled with the fact that we’re not seeing any signs of over expression. So hopefully that gets at your question, Jim.
Operator: [Operator Instructions] The next question comes from Silvan Tuerkcan from JMP Securities. Please proceed with your question.
Silvan Tuerkcan: Thank you very much for taking my questions and congratulations on the great update here. Just considering this is one single trial site and one investigator, can you just comment on the objectivity and variability of especially autonomic function measures? I would assume that they’re measured by some sort of scale a device. How does the breathing pattern, how is it measured, how does it improve? And also the sleep quality and duration. I think that’s a very important measure here.
Sean Nolan: Yes, I would just say that there’s a lot of — both of those functions are measured via different scales and by different people. Some of them are going to be measured like the CGI-I as an example, the R-MBA, that’s going to be measured by the clinician. That’s her clinical observations of what’s happening during a clinical assessment. Whereas with the RSVQ or the PGI, that’s going to be caregiver administered, and they’re going to log that in and demonstrate what they’re seeing there. And then we do have examples like when we look at motor function like the hand function is a good example, right? That’s being videotaped and sent to an independent party to review and score that. So Suku, I’ll turn it over to you to add more color.
