Exsilio Therapeutics, a biotechnology startup led by a former Moderna executive, emerged from stealth Tuesday with an approach it claims can solve some of the shortcomings of genetic medicines.
The Boston-based company is debuting with $82 million from a group of investors that include Novartis’ venture arm and the gene editing biotech CRISPR Therapeutics. It’s led by interim CEO Tal Zaks, who was Moderna’s chief medical officer when the company successfully developed a messenger RNA-based vaccine for COVID-19.
According to Zaks, Exsilio is taking a page from that endeavor. It aims to use mRNA, as well as other tools, to make medicines that can effectively paste entire genes into cells and be administered more than once. The goal is to broaden the reach of gene-based drugs in a scalable and more efficient way.
“We are leveraging what Moderna has demonstrated to work and extending the payload of what can be therapeutically accomplished with the flexibility of mRNA as a new class of medicine,” Zaks wrote in an email to BioPharma Dive.
Exsilio, which is Latin for “leap,” aims to do so by turning to so-called genetic elements, encoded in mRNA and delivered into the body via fatty bubbles known as lipid nanoparticles. These genetic elements, Exsilio says, would be programmed to then insert new DNA into cells’ genomes at “safe harbor” sites that wouldn’t cause unintended harm.
Exsilio believes this approach could allow it to treat a disease regardless of the specific genetic mutation that caused it. Such flexibility would be valuable, as some inherited conditions are linked to many different mutations. The effects of Exsilio’s medicines would durable, the company claims, because the inserted genes would be integrated into a cell’s genome, rather than transiently expressed.
Tal Zaks, the former chief medical officer of Moderna, is interim CEO of Exsilio.
Permission granted by Exsilio
The company pitches its method as a way to sidestep the limitations of viral delivery systems that are commonly used for gene replacement therapy. For example, adeno-associated viruses are too small to contain some large genes and can trigger the body’s defenses, leading to side effects or compromising treatment. Some people already have immunity to certain AAVs, too, or develop it after receiving an AAV-based therapy, making retreatment riskier.
By contrast, Exsilio says its therapies will be able to be given more than once. “We should be able to dose patients regardless of their pre-existing immunity as well as repeatedly until the desired therapeutic gene dosage is obtained,” Zaks wrote.
Exsilio is targeting genetic conditions, cancer and autoimmune diseases. The financing will help the company progress to the point of selecting its lead candidates, though it didn’t say when it expects to bring a prospect into human testing.
Novartis Venture Fund and Delos Capital co-led the Series A round, which involved other investors such as OrbiMed and a J.P. Morgan division’s new life sciences fund. The company was founded in 2022 and seeded by OrbiMed.
“We were captivated by Exsilio’s genomic medicines approach that stands to enable large-gene integration in a safe and redosable manner,” said Aaron Nelson, a managing director of Novartis’ venture fund, in a statement.
Exsilio is one of many biotechs working to broaden the scope of genetic medicines with the help of newer approaches. In recent years, well-funded companies like Prime Medicine, Tessera Therapeutics and Tome Biosciences have launched with similarly large ambitions.
“It is difficult to compare very early technology — the proof will be in the medicines that companies are able to develop for patients,” Zaks wrote.
