With $40M for Exonics, Duchenne’s Gene Therapy, CRISPR Race Heats Up

Xconomy Boston — 

Exonics Therapeutics, one of the players in an emerging race to use gene therapy or gene editing techniques to treat Duchenne muscular dystrophy, has just landed a big round of funding to take its first treatment into clinical testing.

The Cambridge, MA, company, seeded last year by a subsidiary of the nonprofit group CureDuchenne, will use a $40 million Series A round led by The Column Group to advance a Duchenne treatment using the gene editing technology CRISPR-Cas9.

Patients with Duchenne, who are primarily boys, lose the ability to walk by their teens, and often die from complications like respiratory or heart failure at a young age. Over the past year, two treatments have been approved—eteplirsen (Exondys 51), from Sarepta Therapeutics (NASDAQ: SRPT), and deflazacort (Emflaza), now owned by PTC Therapeutics (NASDAQ: PTCT)—but neither are cures. Sarepta’s drug is approved for a subset of Duchenne patients, roughly 13 percent with a specific genetic malfunction, for which it is supposed to slow the progression of the disease. Deflazacort is a muscle-boosting steroid already widely available in other countries, also meant to help slow Duchenne.

Companies and academic institutions have been increasingly investing in gene therapy and gene editing techniques, however, hoping for a potentially much longer lasting solution. The methods would supply genetic instructions for a patient’s body to produce a muscle-protecting protein, dystrophin, that people with Duchenne lack.

Two Boston-area companies, for instance, are on the verge of advancing experimental gene therapies for Duchenne into clinical testing. By the end of 2017, Sarepta will begin Phase 1 studies for two different gene therapies that originated at Nationwide Children’s Hospital in Cleveland. Solid Biosciences, a privately held company that raised $50 million earlier this year, also expects to begin testing of a gene therapy that was licensed from the University of Missouri.

The newer CRISPR-Cas9 technology—a method of performing genetic surgery—has increasingly been harnessed by academics, and now companies, as another possible method to treat Duchenne as well. In 2015 and 2016, scientific groups at Duke University, Harvard University, UCLA and the Broad Institute of MIT and Harvard, as well as Olson’s team at UT Southwestern, published papers in peer-reviewed journals on preclinical CRISPR-Cas9 work. Publicly traded CRISPR drugmakers Editas Medicine (NASDAQ: EDIT) and CRISPR Therapeutics (NASDAQ: CRSP) are each advancing preclinical programs for Duchenne.

Privately held Exonics is in the mix as well. The company is based on the work of of University of Texas Southwestern Medical Center molecular biologist Eric Olson. The experimental treatment uses an adeno-associated virus—a commonly used delivery tool for gene therapy—to deliver a CRISPR gene editing tool into the body. CRISPR-Cas9 is essentially a pair of molecular scissors guided to a cell’s nucleus by a strand of RNA, where it snips out a defective gene—in Exonics’ case, a mutation that prevents the production of dystrophin—and replaces it with a functioning one. The approach, if ultimately successful, could lead to a treatment for up to 80 percent of Duchenne patients, Exonics has said. But CRISPR-Cas9 is only beginning to be utilized in human therapeutics in diseases like genetic blindness in cancer—Editas could begin the first CRISPR trial by a U.S. company next year. Exonics didn’t say how far it is from human clinical testing.

John Ripple, the former CEO of Ensemble Therapeutics, stepped in as CEO of Exonics in September. As part of today’s financing, Column Group managing partner David Goeddel and principal JJ Kang will join Exonics’s board of directors.