• Vertex will spend as much as $2 billion to join a growing list of biotech companies seeking to develop gene therapy for muscular dystrophies, announcing Thursday it will expand a partnership with CRISPR Therapeutics and buy privately held Exonics.
• It’s a particularly sizable investment, as research at both CRISPR and Exonics into muscular dystrophy treatment remains preclinical. Unlike others currently in the space, though, Vertex’s focus is on gene editing via CRISPR rather than the gene transfer strategies now favored by Sarepta Therapeutics, Pfizer and Solid Biosciences.
• In addition to the two deals, Vertex also announced former Audentes executive John Gray as its head of genetic therapies, and said it will establish a new site in the Boston area to house its gene therapy research.

Alongside sickle cell disease and beta-thalassemia, muscular dystrophies have become an attractive target for companies working in gene therapy.

Duchenne muscular dystrophy, in particular, is the focus of a half dozen companies’ research, with Sarepta, Pfizer and Solid considered the most advanced. Vertex’s entry, by way of CRISPR and Exonics, adds another well-respected biotech to the mix.

Duchenne, or DMD, is one of the more common and severe forms of muscular dystrophy, and almost exclusively affects boys. Most of those affected don’t live past their mid-twenties, and progressive muscle weakness means many require a wheelchair as the disease advances.

Treatment options remain limited, with Sarepta holding the most recent DMD approval for its controversial drug Exondys 51 (eteplirsen).

Experimental drugs from Sarepta, Pfizer and Solid propose a genetic fix for the mutated dystrophin gene behind the disease. By delivering a functional copy of gene to muscle tissue — an approach known as gene transfer — the companies aim to spur production of the needed dystrophin protein that’s missing in DMD patients.

Vertex’s approach with CRISPR and Exonics will be different, relying on CRISPR gene editing to repair DMD-related mutations in the body and thereby restore dystrophin production.

The biotech, which is best known for its trio of cystic fibrosis treatments, will pay a substantial sum to enter the space, however.

Under deal terms with Exonics, Vertex will acquire all shares of the private company for $245 million upfront, and as much as $755 million in milestone payments.

CRISPR and Vertex are already working together, having partnered in 2015 in sickle cell and beta-thalassemia. The first patient in a Phase 1 study of the CRISPR-based gene editing therapy covered by that deal was treated in February.

Expanding the CRISPR partnership into DMD and myotonic dystrophy Type 1 (DM1), another research focus, will cost Vertex $175 million upfront and potentially up to $825 million more.

Such financial commitment shows “a real appetite to pursue non-small molecule R&D,” wrote Stifel analyst Paul Matteis in a note to clients. Small molecules like Vertex’s cystic fibrosis drugs have to date been the company’s strength.

Per the agreement with CRISPR, Vertex will hold exclusive rights to both the smaller biotech’s existing and future IP concerning the use of CRISPR and related delivery platforms for DMD and DM1 gene editing candidates.

Exonics is centered on the research of Eric Olson, a professor at the University of Texas Southwestern Medical Center.

The company raised $40 million in Series A funding in late 2017 and has attracted the likes of Merck & Co.’s Roger Perlmutter and the noted gene therapy researcher Jerry Mendel to its corporate and scientific advisory boards.

CureDuchenne Ventures, the investment arm of the similarly named patient group, helped found Exonics in 2017.

So far, Exonics has only researched its approach in mice and dogs. Results from the latter group of animals showed Exonics’ gene editing therapeutic restored dystrophin expression in skeletal muscle tissue of up to 90% of normal.

DMD gene therapies with clinical data, meanwhile, have had mixed results.

Sarepta widely impressed last year, showing that four boys treated with its microdystrophin gene therapy could stand up, walk and climb stairs more quickly than normally would be expected.

Readouts from Solid, though, were less encouraging. Phase 1 data are expected from Pfizer later this month.