- CEO Michael Ehlers
- Total raised $90 million
- Headquarters Boston, MA
Ascidian Therapeutics has a secret list of nearly 400 diseases that its gene-altering technology might help cure. But you’ll only find one listed on their website. And so far, that single-mindedness is paying off.
Earlier this year, the Boston-based biotech became the first company to receive the FDA’s blessing to begin a clinical trial of an RNA editing therapy in the US. Ascidian is one of several small biotechs designing therapies that change the code of short-lived messenger RNA molecules, rather than permanently altering DNA.
And while most RNA editing companies are trying to make single-letter changes to genetic code, Ascidian has devised a way to swap out large swaths of RNA, spanning hundreds to thousands of letters. It’s a search-and-replace tool for RNA that could treat many diverse causes of a genetic condition with a single therapy.
“We were highly aware of all the other things going on,” CEO Michael Ehlers told Endpoints News. “We wanted to leapfrog all of that.”
Ascidian hasn’t made as big of a splash as other startups in the gene editing field, in part because its $90 million in funding from Apple Tree Partners and single disclosed program feels modest compared with the hundreds of millions of dollars that other gene editing startups have raised for pipelines spanning a dozen diseases or more.
The startup currently has about 40 employees, and Ehlers doesn’t anticipate getting much bigger. “Our philosophy is focus,” he said.
Its lead target is treating an inherited form of vision loss called Stargardt disease. The cause of the condition is well-known. Any one of more than 1,000 different mutations in a gene called ABCA4 can cause progressive death of photoreceptors in the eye, often in children and young adults.
In theory, replacing the whole gene should treat the condition. But ABCA4 is simply too big to fit into the viral vectors commonly used in gene therapy. And using gene editing to fix each of the many DNA mutations is impractical. Instead, Ascidian designed a single therapy that replaces a large swath of the RNA where roughly two-thirds of mutations arise.
The company is currently enrolling 13 patients in its Phase 1 clinical trial. It’s primarily focused on safety, but Ascidian will also monitor the vision-robbing lesions in the back of the eye. Although Ehlers doesn’t expect to restore vision that’s already lost, he hopes to dramatically slow, and maybe halt, the disease.
“Coming out of it I think we will be able to say quite a bit on the efficacy signals and safety of the drug,” Ehlers said.
Ascidian has yet to publish or present details on exactly how its RNA editing works — another reason it has kept a low profile — but CSO Robert Bell explained that it hijacks the familiar cellular process called RNA splicing.
RNA molecules are like photocopies of the DNA master file. But before cells can use them to make proteins, they must remove genomic fillers and stitch together the actual code, regions known as exons. Normally, this splicing occurs within a single molecule. But some organisms — including ascidians, better known as sea squirts — can swap exons between different RNA molecules in a process called trans-splicing.
Partly inspired by those squishy marine animals, Ascidian’s technology uses an RNA molecule to trigger trans-splicing at will. Its Stargardt therapy replaces the first 22 of 50 exons in the ABCA4 gene where the majority of mutations arise. If the approach works, the company could make a second therapy to address mutations in the remaining exons, Ehlers said.
Ascidian’s origins trace back to a 2018 paper from University of Pennsylvania scientist Jean Bennett, who developed the RNA editing approach for a different rare form of vision loss. Her technology was first licensed to Limelight Bio and then spun out into Ascidian in early 2020 before Limelight shut down.
Since then, Ascidian has worked to improve the rates of RNA editing to as much as 80% in some applications, Ehlers said.
As for what’s beyond Stargardt, the company isn’t saying much. The startup recently struck a partnership with Roche worth $42 million upfront and as much as $1.8 billion in milestone payments, with a focus on unnamed neurological diseases. The startup won’t say how long its current funding will last, but chief financial and business officer Daniel Rosan said that “a significant amount” of the Roche partnership is in potential near-term payments.
“And because the application of the tech is so broad, we are entertaining other partnerships,” he said.
Key backer: Apple Tree Partners
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