And if you look at the 17 to 20 year old group that for phenotype study that drop in the RSBQ only 2 points. So I guess in relative terms, even though I don’t like doing cross study comparisons, our first patient showed a 22 and a 23 point drop and the second patient who has much milder disease at a 4 point drop.
Gil Blum: The severity was…
Sean Nolan: And the severity, that’s right.
Gil Blum: And I agree this is very early. This is more for educational purposes. My second question, so kind of as a segue in a hypothetical adult study, would it be beneficial to look at patients with more severe disease just to increase the signal to noise?
Sean Nolan: Yes, you’re saying, basically enrich the study with more severe patients to show a bigger effect. You know what’s interesting, Gil, when you look at the phenotype data, they generated their P-value difference essentially off the severe patients. But there really wasn’t much effect in CGI-I or RSVQ and mild to moderate. So your point’s a good one. I think, what’s exciting us and we have to see more patients, I think to get to a more definitive answer. But what we liked about this was the fact that the genotypes were so different and the corresponding phenotypes were so different, yet we’re still seeing response is very encouraging that, again, the population that could be treatable here continues to remain significant. So I would say, to reaffirm Suku’s point, let’s see some more patients, let’s get to the high dose as well. And that’ll certainly inform how we think about Part B endpoints and trial design.
Operator: The next question comes from Yanan Zhu from Wells Fargo Securities. Please proceed with your question.
Yanan Zhu: So, I have a question on R-MBA and I think, if I heard this correctly, I think the patient number two’s R-MBA improvement is roughly 7 points. And that sounds like, that’s as big as patient number one’s 12 week improvement and much bigger and bigger than patient number one four week improvement. If you comment on why despite of the milder disease in this patient R-MBA improvement appears to be quite striking? And if you can provide the baseline R-MBA score for this patient that would be great. And I have a maybe one or two follow ups.
Sean Nolan: So, the baseline scores to your point were for patient one was 43, for patient two is 38, and then at week four for patient two is 31, week four for patient one was 48, and now at week 12 patient one’s at 37. So, there’s been a 6 point drop in patient one over 12 weeks and a 7 point drop in patient two over four weeks. And then, I’ll turn it over to Suku to try to get at the rest of your question. What was driving this?
Sukumar Nagendran: Right. So that’s an important question because R-MBA is a clinician assessment of the patient as well, and it has five components and I think goes up to a score of as you can see on the scale. The first patient who was much sicker, these R-MBA score was influenced by anxiety, right, and fear and also increased paroxysm, right, which shifted the score in a manner that didn’t show improvement. But actually, when we talked to some of the experts, the understanding was that increased muscle function in the face included the maceta muscles where there bruxism is actually positive. But in the assessment of these questions that were set up, as I said, they were arranged and designed to actually show disease worsening, not necessarily a therapeutic response.
And to my knowledge, R-MBA has never been validated to evaluate a therapeutic intervention. In patient two though, given that this patient had much milder disease, the change I think is positive because this patient already did not have some of the previous abnormalities of severe patients such as patient one hand. And therefore, the questions asked in the R-MBA didn’t cloud the actual assessment. So, I guess my point again is that you need to really understand what the questions are within some of these measures to make sense of the eventual numbers. And Kamran, do you want to comment on that or?
Kamran Alam: So, in terms of provide the motor behavior assessment some of the improvements were in social skills and respiratory behavior.
Sukumar Nagendran: So, I guess if I can add one punctuate that point though, what I would also say is that the clinical assessments of each of these patients, especially hopefully for a transformative therapy, will significantly overcome sometimes the need for these skills that mostly have not been validated for therapeutic intervention and assessment.
Yanan Zhu: Thank you, and then — I’m sorry, my follow up is that for the 4 point improvement RSBQ, which sounded like similar to Treg phenotype, what Treg phenotype can achieve, but it is also on the other hand, sounds like the patient had many improvements clinically. Could you comment on what could the improve the nature of the improvement differ in what you saw in this patient compared with if this patient had been treated with Treg phenotype for example? And maybe lastly, about patient number three, I was just wondering, have you identified that patient, if so, how severe that patient is? Thank you.
Sean Nolan: I would say, with the Treg phenotype piece of the question, when you look at patients that had moderate or mild disease, the impact on RSBQ was 1. So in this particular circumstance, you would definitely grade this person out as a mild or moderate and the impact that we demonstrated was 4 on that particular scale. And as we said, it was driven primarily by the breathing, the socialization and the gross and fine motor skills. So, it’s very consistent with the feedback that that’s being put forward by the physician and her assessments and observations by the parents and their assessments and observations. And where she’s landing is 33, which is in the same ballpark at week 12 is where the first patient is landing, which is at 30.
So, it looks like we’re getting a very nice response from her. And again, I think the Suku’s point, the scales I think to me are becoming. It’s good to see correlation that the scales are moving in the right direction along with what’s being observed clinically. And we’re seeing a lot of congruence across clinical domains, which I think is a testament to the product getting to where it needs to be levels of MECP2 being put forward into a more therapeutic area and which is why we’re seeing some comprehensive behavior across the table. As it relates to patient number three, I would say that we have identified the next adult patient. She has not yet gone through screening and there’s a couple things at play which is why we modified the guidance to Q4 this year.
Q1 next year dosing is that it’s final stages of an LAR process, which we’ve talked about in the past, which we don’t have absolute line of sight to, so we know it should be in that window. And within the institution there’s windows of time given the holidays and what have you — where the patient can slot in. So, it is still possible this year could be Q1 next year. We’ll keep you apprised on that, but we do not know any baseline characteristics at this particular juncture. We just do know that it would be a stage four patient.
Operator: The next question comes from Jack Allen from Baird. Please proceed with your question, Jack.
Jack Allen: I was hoping you could provide some more context around the steroid regimen that’s given post dose here and how the results from patient one or shaping up in the context of the steroid taper? So, what degree of confidence do you have that these results are different from potential? Any potential impact that could be due to steroids in the short term post gene therapy?
