Update on IDefine Research Program

The rare drug development process can be painstakingly slow and frustrating. However, there is reason for real optimism in the Kleefstra Syndrome community.

The Ultragenyx Rare Bootcamp attended by IDefine CEO Geoff Rhyne and Chief Scientific Officer Eric Scheeff provided additional clarity on the Research Roadmap to a treatment, and IDefine is making moves.

“It was emphasized by those who have gone before us in the rare drug development process the importance of not only working on the next step, but to also be thinking about future steps and to be putting the pieces in place for those, and that’s what we’re doing,” said Scheeff.

IDefine continues to gather Research Assets, the initial step on the path. Each Research Asset listed on the graphic above has an asterisk next to it because each is dependent on community participation. Families can help advance research by signing up for things like AllStripes, Rare-X and the Kleefstra Syndrome World Map.

Research Focus

The next big step falls under Preclinical Research and includes selecting an approach to a treatment. After extensive investigation and months of discussion with its Scientific Advisory Board (SAB) and other experts, IDefine has narrowed its current focus to gene therapy and antisense oligonucleotides (ASOs).

“You can’t take all of the shots on goal that you would like, you have to pick what shots you’re going to take,” said Scheeff. “We’re prioritizing based on talking to the very best experts in the rare disease field, by digesting a ton of information and by evaluating what approaches have already been tried for KS and similar conditions.”

People with Kleefstra Syndrome have one good copy of the gene EHMT1 but are either missing or have a mutation in the other copy. In very basic terms, the goal with gene therapy is to deliver another healthy copy of EHMT1 so there are two copies.

ASOs are special molecules because unlike, regular drugs, they can target one gene specifically and control the output of that gene by either turning it up or turning it down. With KS, since every patient has one good copy of EHMT1, if you modulate the output of that gene by “turning it up” with an ASO, you can potentially impact the disease by giving the patient back more of what’s missing.

Reason for Hope

Angelman Syndrome is like KS in that it is caused by the loss of function of one copy of a single gene. Angelman Syndrome is currently in a clinical trial using an ASO to upregulate the copy of the gene that is turned off in the syndrome.

“This isn’t 20 years ago where this stuff wasn’t possible, the landscape has shifted,” said Rhyne. “There are some definitive opportunities to explore. It doesn’t guarantee success, but we feel like this is a big opportunity worth spending energy on.”

And KS is better positioned than many other conditions to move forward.

“We know out of the 10,000-plus rare diseases, with KS we have a very well understood, well studied gene that you don’t always have,” said Rhyne. “We have a target. There isn’t any mystery around that. We know what we’re trying to fix, we just have to figure out how.”

Despite that knowledge and the research advances, gene therapy and ASOs are still relatively new and highly technical science that comes with no guarantees. Therefore, IDefine’s SAB continues closely evaluate the options.

“We know that funding is precious, and we want to make sure we spend it in the most efficient way that gives us the highest probability of the outcomes that we’re hoping for,” said Scheeff. “It’s worth doing the work on the front end to raise our odds.”