Vertex Pharmaceuticals didn’t have to look far to find its next drug program. The Boston biotech company — one of the state’s largest and most profitable — has struck a collaboration with its next-door neighbor Entrada Therapeutics to develop genetic therapies for a rare muscle disease.
Entrada will earn $250 million at the outset of the four-year partnership with a $224 million upfront payment and $26 million equity investment from Vertex. Depending on the success of the program, the 125-person biotech firm could receive up to $485 million more in milestone payments, plus royalties.
The companies are both based in the Seaport neighborhood, with Entrada’s headquarters planted right behind Vertex’s newly opened cell and gene therapy center in the Raymond L. Flynn Marine Park, where Entrada is working on its own genetic therapies for muscle diseases.
The partnership is focused on, but not limited to, an experimental drug that Entrada was already developing for myotonic dystrophy type 1, often called DM1. The inherited condition causes muscle weakness and can also impair other organs including the heart, lungs, and digestive system. The disease afflicts more than 90,000 people in the United States and Europe, according to Entrada.
There are no treatments that address the genetic cause of the disease, but not for want of trying. A decade ago, Cambridge-based Biogen and California-based Ionis Pharmaceuticals formed a partnership to develop a genetic therapy for DM1, but the program was dropped after lackluster results. Vertex is betting that Entrada’s approach will lead to a different outcome.
Vertex is Boston’s biggest biotech company by market capitalization with a total stock value exceeding $81 billion. The company expects to earn up to $8.9 billion from sales of its cystic fibrosis therapies this year. And with little competition for that drug franchise in sight and nearly $10 billion in cash on hand, investors have been eagerly awaiting the company’s next moves.
Yet like many pharmaceutical firms this year, Vertex has opted to partner with, rather than outright acquire, a smaller biotech. Still, the deal with Entrada is one of the largest upfront payments this year for a partnership on a drug not yet in clinical testing.
The drug is a synthetic genetic molecule — known as an oligonucleotide — similar to Biogen’s therapy for spinal muscular atrophy, Spinraza. Entrada’s treatment is designed to target, block, and degrade bits of repetitive and errant genetic code that disrupt normal genetic processing in cells and damage muscles. By removing these toxic molecules, the company hopes to help DM1 patients maintain muscle function.
Entrada previously said it plans to go to the FDA in the second half of 2023 for permission to begin a clinical trial of the drug. Vertex will now be responsible for clinical trials of the drug as well as manufacturing and commercialization.
Waltham-based Dyne Therapeutics already has an oligonucleotide therapy for DM1 in early clinical trials. Several other firms, including Cambridge-based PepGen and California-based Avidity Biosciences, are developing their own genetic therapies for the disease.
Entrada was founded in 2016 based on the belief that new drug delivery technologies were needed to realize the full potential of modern medicines, including oligonucleotide therapies. Many drugs based on genetic molecules or proteins can’t easily wiggle their way into cells, and even if they do, they are quickly encapsulated and destroyed by a structure called an endosome.
To overcome that problem, Entrada has developed a chemical modification it can add to genetic or protein therapies to help them get into the cell and escape from the endosome intact. The company raised more than $175 million from private investors for the technology before netting an additional $190.7 million during its initial public offering late last year.
The company is working on eight preclinical drug programs, with a focus on neuromuscular diseases, including therapies for multiple forms of Duchenne muscular dystrophy, or DMD.
Before the Entrada partnership, Vertex had its own research programs to design CRISPR gene editing therapies for both DM1 and DMD, including through a partnership with the Boston firm CRISPR Therapeutics. Details on the progress of those programs remains scant.
Ryan Cross can be reached at ryan.cross@globe.com. Follow him on Twitter @RLCscienceboss.