Vertex eyes Duchenne market with Exonics, CRISPR deals

Vertex Pharma has agreed a pair of deals to build a position in gene-editing therapeutics for diseases like Duchenne muscular dystrophy.

First up is a deal to acquire US biotech Exonics Therapeutics, which is developing gene-editing therapies for DMD and other genetic neuromuscular diseases including myotonic dystrophy type 1 (DM1). Vertex is paying $245m upfront for the CRISPR/Cas9-focused company with another $750m or so in the offing in milestone payments.

Vertex is also paying $175m upfront to expand its collaboration with Swiss company CRISPR Therapeutics, with milestones that could drive the value of the deal above the $1bn mark. That deal also focuses on gene-editing technology directed at DMD and DM1.

To bring the two elements together, Vertex says it plans to set up a new genetic therapies research site in the Boston area, and has appointed John Gray, previously chief scientific officer of neuromuscular and liver disease gene therapy player Audentes Therapeutics, to lead the effort.

DMD is a rare muscle-wasting disease that mostly affects boys and is caused by a defect in the gene coding for dystrophin, a protein found in muscles that is critical for movement. It affects some 300,000 people worldwide and is typically fatal by age 30. DM1 is the most common adult muscular dystrophy, and is also caused by dystrophin gene mutations.

The move extends Vertex beyond its main activities in cystic fibrosis, which have resulted in a clutch of marketed products that have transformed CF care but also attracted no little controversy over pricing, and early-stage projects in pain, haemoglobinopathies and alpha-1 antitrypsin deficiency (AATD).

The push into DMD sets the company up in opposition to Sarepta Therapeutics, which sells its exon-skipping therapy Exondys for DMD in the US but has been unable to get it cleared for the EU market, and is also preparing to file a follow-up therapy in both markets.

It will also face competition from a growing list of DMD gene therapy developers, which along with Sarepta also includes Solid Biosciences – which reported disappointing data with its candidate earlier this year in a phase 1/2 trial – as well as Pfizer and Audentes.

Vertex's track record in bringing genetic therapies to market stands in its favour. Its CF drugs Kalydeco, Orkambi and Symdeko/Symkevi collectively brought in $857m in sales in the first quarter of the year, up more than a third despite payer resistance in some countries, including the UK.

Jeff Leiden

“We are bringing together the intellectual property, technologies, and scientific expertise needed to establish a leading gene editing platform for DMD and DM1,” commented Vertex’s chief executive Jeffrey Leiden.

He added: “We are continuing to build a toolbox of small molecule and nucleic acid technologies and capabilities that will allow us to drive scientific innovation to produce transformative medicines for a broad portfolio of diseases.”