Exsilio launches with $82M for redosable gene therapies

A signature trait of the limited gene therapies currently approved is their single-dose administration. However, Tal Zaks, interim CEO and chair of Exsilio Therapeutics, argues that this characteristic is actually a drawback rather than an advantage. Exsilio Therapeutics, based in Boston, has recently emerged from stealth mode with $82 million in funding to develop redosable gene therapies utilizing mRNA and lipid nanoparticle (LNP) technologies.

Zaks, who identifies as a dedicated R&D enthusiast, mentioned that the recent funding round became necessary after the company produced compelling data that warranted a shift from a primarily research-oriented focus to development, essentially laying the groundwork for a pipeline of potential medications. The financing was co-led by Novartis Venture Fund and Delos Capital, with additional contributions from OrbiMed, Insight Partners, JP Morgan Life Sciences Private Capital, CRISPR Therapeutics, Innovation Endeavors, Invus, Arc Ventures, and Deep Insight.

Exsilio aims to develop genomic medicines targeting autoimmune and genetic diseases, as well as cancer. These medicines will be based on “naturally occurring, programmable genetic elements” encoded in mRNA and delivered via LNPs. Zaks explained that while the potential for curative treatments in gene therapy is widely recognized, the challenge lies in delivering these treatments both effectively and safely. Current therapies are restricted to a single administration because they employ viral vectors for delivering genetic material. Patients can develop antibodies against these viral vectors, rendering a second dose ineffective if the initial therapy's effectiveness diminishes. Additionally, these therapies lack precision in ensuring the genetic material reaches the intended location in the genome.

An exception to this is Krystal Biotech’s Vyjuvek (beremagene geperpavec), a redosable topical gene therapy for dystrophic epidermolysis bullosa, which utilizes a genetically modified herpes-simplex virus. Exsilio is keeping many details of its technology confidential, but Zaks described it as the "missing link" between DNA encapsulated in viral vectors and mRNA editing tools, which are adept at making small DNA changes but struggle with incorporating entire genes.

Exsilio’s approach relies entirely on mRNA, meaning their elements are proteins or elements that encode mRNA. The key is to incorporate elements that facilitate the insertion of a gene transcribed into DNA. The ultimate objective is to create a therapy capable of inserting an entire gene into a safe locus in the genome, leading to a corrective or therapeutic effect. This therapy should also be adjustable in dosage and capable of being administered multiple times if necessary.