November 5, 2025
Dear IQSEC2 family
Update on new developments in the first clinical trial for IQSEC2 in boys with knockout
mutations and a second trial we are now planning for girls and also in the remaining
boys with class 2 mutations (not knockout).
Clinical trial in boys with knockout mutations.
Pleased to report on a very productive meeting in BioEurope in Vienna where we met
with many groups that will help facilitate the clinical trial and the different components that need to be coordinated -regulatory issues with the European Medical Association, upscaling production of the virus for human use and contracting with a clinical center in Europe where we will conduct the clinical trial. Things are moving quickly, and we hope that within 1 year we will be able to have our first child treated. There remain many details that will be resolved soon such as which clinical center. Regarding the selection of the boys for the trial this will be done by a clinical advisory board of 4-5 neurologists that will select which of the eligible boys will be in the first trial. I want to emphasize we aim to treat everyone, but we need to be successful in this first trial in order to be able to generate funding for a larger trial in more children and to help persuade governmental authorities that compensation for this treatment is warranted. We will be completely transparent in this process, but it is still too early to discuss which children will be selected for this first study.
Clinical trial in girls with IQSEC2 mutations (knockout) and in boys with class 2
(gain of function mutations)
We have received many inquiries regarding whether we hope to also treat girls as the
first clinical trial is targeting boys with knockout mutations (class 1 mutations). This is
simply because the treatment of the boys with knockout mutations is more
straightforward involving replacement of the entire gene and, as will be explained below, treatment of the girls due to their heterozygous state and the remaining boys will require an additional twist in the treatment -however we believe we have identified the way forward for the girls and the remaining boys.
Previously I wrote about one approach for the girls which we are pursuing-involving a
knockout of the existing IQSEC2 and replacement with the normal IQSEC2. This research is ongoing. What is very new and exciting is the idea of applying gene editing
as an alternative approach-new developments in gene editing are making it possible to edit specific mutations in cells which do not divide (such as neurons). There are various editing strategies which perhaps we will explain in a webinar soon but
essentially the gene editing approach is one we are now pursuing aggressively and are
quite optimistic based on success in other diseases. The caveat is that gene editing in
its current form requires that the correction for each mutation be different and
personalized for each child’s mutation. This is not particularly complicated but will
require optimization for each mutation in the lab and also may require additional
regulatory steps although this will be discussed with the regulatory authorities (EMA).
We are very excited about this opportunity which we will be doing in collaboration with
other labs around the world. It is too early to say when we will be able to launch a trial
using gene editing in the girls (and the remaining boys which may be treated in the
same way) but the field is moving very rapidly, and new discoveries may even make the
caveats, that I mentioned above, moot within the next 6 months. Bottom line: we are
not going to leave any child behind and want to work on developing a therapy for all kids with IQSEC2 mutations-it is becoming clear that the therapy will need to be tailored to the type of mutation which brings some complexity, additional costs and time to the development of these therapies.
Wishing all of our community good health and strength
Andy
Professor Andrew P Levy MD PHD
Technion Faculty of Medicine
Haifa ISRAEL
