Emendo Eyes the Clinic for CRISPR Therapy That Makes Single-Gene Edits

Xconomy New York — 

CRISPR gene editing offers the potential to selectively edit the genetic mutations causing inherited diseases, but Emendo Biotherapeutics CEO David Baram contends it’s not precise enough. A large number of genetic diseases can’t be addressed by current CRISPR approaches and the technology still raises safety concerns.

Emendo is developing a way to make CRISPR gene editing more precise, addressing more genetic disorders while also avoiding unintended edits that can lead to toxic effects. Last week the New York-based biotech closed a $61 million Series B round of financing, cash that Baram says will help the company bring its gene editing approach into tests in humans some time next year.

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Emendo aims to treat dominant genetic diseases, which are caused by a mutation to one allele, or copy of a gene. Fixing those diseases requires a gene-editing therapy that limits its edits to the mutated copy. Baram says current CRISPR technologies cut both genes, which could make the disease worse or cause other unintended effects.

“You want to knock out only the toxic allele and leave the other one intact,” he says. “The thing is it requires a high degree of specificity.”

That specificity comes from nucleases, the cutting enzymes that snip the DNA strands so they can be edited. The Cas9 enzyme is one nuclease commonly used in CRISPR editing. Emendo is designing other nucleases. Not all nucleases work on all cell types, so Emendo is working with a library of these enzymes. Baram says Emendo’s OMNI technology can engineer nucleases so that they edit on a specific site in a specific gene in a specific cell. He adds that this approach enables Emendo to develop gene-editing therapies to edit any site on the genome and address dominant genetic diseases, which represent the majority of inherited disorders.

Emendo was founded in 2015 by Baram and a group of scientists from the Weizmann Institute of Science in Israel. Baram, whose background includes research in structural biology and protein engineering, says the scientists were trying to “expand the boundaries of gene editing.” The Emendo technology was developed in-house.

The company’s drug pipeline includes a preclinical treatment for severe congenital neutropenia, a condition that leads to a deficiency of neutrophils, a type of white blood cell. Patients who have the disorder are prone to recurrent infections. The company has additional preclinical therapies for primary immunodeficiency and bone marrow failure.

A number of companies are pursuing “next generation” approaches to gene editing. The base editing technology of Beam Therapeutics offers the potential for editing a single strand of DNA, avoiding the double-stranded breaks that can lead to unintended effects. In September, the Cambridge, MA-based company filed for an IPO. The same month, South San Francisco-based Trucode Gene Repair closed a $34 million Series A round of funding to continue development of its technology, which uses a nanoparticle to deliver a DNA sequence to its target and potentially avoid the off-target effects that can occur with CRISPR editing.

To date, Baram says Emendo has raised $73 million. Besides supporting plans to bring two therapies into clinical testing next year, the cash will also finance manufacturing and further development of the OMNI technology. Raising more cash depends on whether Emendo strikes up research alliances with large pharmaceutical companies. So far, the startup’s only disclosed partner is Takeda Pharmaceutical (NYSE: TAK), which was one of Emendo’s investors at its start. The latest financing was led by AnGes, a Japan-based pharmaceutical company that Emendo says has expressed interest in a partnership with Emendo.

Until closing the Series B investment, Emendo kept quiet about its research with the exception of posters at scientific conferences. The company has not yet published papers describing its technology, but Baram says that will change this year.

“We have a lot to say, and the scientific world will be interested to hear about it,” he says.

Photo by Flickr user MIKI Yoshihito via a Creative Commons license