Yanan Zhu: Understood. Thank you for the answer. If I may do a quick follow-up question on the Patient 1, Patient 2 in the adult data set. We can see clearly patient 1 has continued improvement or new improvement in RSBQ. Patient 2 have new improvement in RMBA. But interestingly, the other endpoint for those patients seems to be pretty flat. Do you — so how do you think about that? And is there a potential for the other endpoint to also improve in the future? Thank you.
Sean Nolan: If you’re referring to like CGI-I would say this — is that what you’re talking about?
Yanan Zhu: Sorry, sorry, CGI-I, I fully appreciate even maintenance of the prior numbers according to our check with the doctors, that’s a very, very encouraging sign to have those minimum improved ratings maintained following in a follow-up and also to have the much improved for the other patient maintained. Those are great achievements. I’m talking about RSBQ and RMBA, where both patients had one score improve and the other score relatively flat. Yes, that’s what I’m talking.
Sean Nolan: I got you. So in Patient number 1. So first of all, the RMBA is administered by the clinician in the hospital. The RSBQ is provided by the caregivers in the home setting and they ask different questions, okay? So it’s a little difficult to put apples to oranges. But I would say this, we actually asked the primary investigator this same question. And what she said was the Patient number 1 has gotten very aware of what’s going on in her surroundings. If I showed you the video from pretreatment, she was very, very, almost like in a catatonic state in a wheelchair, really not interacting. Now she’s much more aware. She’s trying to communicate and vocalize. And basically, what the PI told us is she does not like going through the testing at the hospital.
She gets irritated and she doesn’t want to cooperate. And at this point, she has the strength to not cooperate. So that has been driving some of the it’s driving the score that you’re seeing. She’s essentially not necessarily cooperating with some aspects of the disease of the testing, where in the home setting, she’s getting very much a comfortable situation and sees the parents are seeing. The other thing I would say is that some of the improvement that I mentioned earlier in the RSBQ, the patient one had was in the anxiety, the general mood aspect of things, that is not captured in the RMBA. So that’s one aspect there. On Patient 2 her RMBA improved significantly, and it was driven essentially by her socialization, her interest in communicating with people and also her seizures.
Those were big drivers. In the RSBQ, neither of those is addressed. Neither one of those is quantified. And in the RSBQ, again, she had an elevation in anxiety and some of the Niton behaviors, which again — if you think about what I said about patient 1, steroids, that could also be the case. She has had a bit of an issue with tolerating the steroids. So hopefully, again, that gives you some perspective on those two things. And Suku had something to add as well.
Sukumar Nagendran: Yes. And also for Patient 2, I would highlight the seizures were decreased by 95% post gene therapy treatment. So this patient had, I think, eight to 16 seizures a month, and other than one seizure day 13 post treatment, the patient has had no new seizures and also the use of a combination antiepileptic meds have dropped by 25%. That is a big deal from a clinical standpoint and for the parents and caregivers and from an activities of daily living standpoint. The second thing you should note is in Patient 2, some of the hand function and stereotypic movements have decrease, which also makes it promising that this patient may eventually get independent functionality of the hand. And there is something else that goes on in about 40% of these patients with Rett syndrome which is the upper and lower extremities, have abnormal circulation, which means the hands and feet get quite cool and at times painful, and you would note in Patient 2 and Patient 1 that resolve post-gene therapy treatment.
So other than RMB and RSBQ, which obviously we focus on for different reasons, these major clinical observations, I think, could be life changing in this stage of population.
Operator: Our next question comes from the line of Jack Allen with Robert W. Baird. Please proceed with your question.
Jack Allen: All right. Thanks for taking the question, and congratulations on the progress. I’m looking to zoom out a little bit and take attention to the established collaboration that you have. It seems like you’re really developing data quite quickly, especially with the pediatric low-dose data expected in the middle of this year and the potential initial high dose data later this year. Can you remind us of the structure of the Astellas deal and how it relates to the rep program? And what measures are in place to ensure you get a fair deal. I believe the option was fairly open-ended when that deal was struck?
Kamran Alam: Yes. I mean essentially, what Astellas has is a right to negotiate an option with us, an exclusive right that they have there’s no predetermined terms to your particular point. The option period gets triggered after a number of — about a handful of pediatric patients have, call it, six months of data or so. So there’s no time punch at this particular point in time. Where Astellas has to come in and either request an opt-in or not, that’s likely a 2025 topic. The other point that I want to really stress is that Astellas certainly has line of sight to things, but it doesn’t — the agreement itself doesn’t preclude another party who might be interested in the program or in the company from making an unsolicited offer. That’s fine. We would just have to notify Astellas of that and they would have the ability to counter, if you will. But there’s no blocking right in it. Hopefully, Jack, that gives you some perspective on that. Or did you have a follow-up?
