Exsilio Therapeutics has raised $82 million in hopes of using mRNA to surmount the limitations of current gene therapies.
mRNA is a medium that the biotech’s chairman and interim CEO Tal Zaks is intimately familiar with. Zaks was Moderna’s chief medical officer from 2015 to 2021, leading the company’s development of its Covid-19 vaccine before becoming a partner at the healthcare investment group OrbiMed.
Exsilio received an undisclosed amount of seed money in 2022 from OrbiMed. Its $82 million Series A raise, announced Tuesday morning, was co-led by Novartis’ venture arm and Delos Capital, followed by OrbiMed, Insight Partners, JP Morgan’s life science investment group, CRISPR Therapeutics and Innovation Endeavors, among others.
“The [gene therapy] field has coined the ‘one-and-done’ idiom. But ‘one-and-done’ is really a bug, it’s not a feature,” Zaks told Endpoints News on Monday ahead of the announcement.
Exsilio plans to use an mRNA-based therapy to insert whole genes, which could potentially be applied across a host of diseases caused by genetic mutations. The mRNA would encode a gene of interest and items to facilitate its insertion, including mobile genetic elements, which could be delivered via a fatty acid bubble called a lipid nanoparticle (LNP).
The mobile genetic elements are where Exsilio derives its name, which is Latin for leap. Mobile genetic elements include a vast library of DNA segments that include plasmids, transposons and integrons, among others, which can move around the genome. The company’s platform uses both computer modeling and wet lab experiments to discover and engineer the genetic elements used to insert genes.
With Exsilio’s technology, a gene would be inserted at a safe harbor site — places in the genome where a gene can be inserted and function, but won’t cause safety risks.
Zaks left much of the company’s science in the dark. He declined to elaborate on the mobile genetic elements, noting that the company still has to “get to a point where we’ve got our IP filed and we can actually show some data that we can talk about.”
He said that Exsilio has a small team in Israel and is building a team in Boston, but declined to share who the company’s founding scientists or scientific co-founders are. On the Israeli-Palestinian War, he said, “These have been clearly difficult times for our team,” but noted the company has maintained “full productivity.”
He also declined to name which exact diseases Exsilio is hoping to work on, but said it could go after “any disease that has been a target for a gene therapy.”
The hope is that an mRNA therapy would come with fewer toxic side effects — akin to the Covid-19 vaccine. While current gene therapies have been life-changing for some, safety issues, such as immune reactions and liver failure, have led to deaths.
“I spent a lot of time in mRNA- and LNP-land and always was skeptical about gene therapies. This is the first time I’m investing a significant chunk of my time in gene therapy,” Zaks said. “Part of it is because I am not just inherently conservative as any drug developer is. I’m also a medical oncologist and so I worry about safety first and foremost.”
Unlike current virus-based gene therapies, an mRNA treatment could potentially be given as several doses, instead of one really high dose, and re-dosed down the line if need be.
Other high-profile biotech companies are also working on gene insertion that borrows from mobile genetic elements, though none have put the technique into human studies yet. Prime Medicine and Tome Biosciences are developing competing but similar platforms that use next-gen gene editing. The gist of their platforms is that they write a short sequence of DNA at a specific site that is recognized by an enzyme called an integrase, which then incorporates a gene of interest at that site.
Zaks said Exsilio is currently in the process of searching for a permanent CEO. With the Series A, Zaks said the company plans to name a development candidate with preclinical data. He declined to say when the company hopes to be in the clinic.