Vertex and Entrada Partner to Discover and Develop Novel Therapeutics for Myotonic Dystrophy Type 1

Vertex Pharmaceuticals and Entrada Therapeutics have entered a global collaboration focused on discovering and developing intracellular Endosomal Escape Vehicle therapeutics for myotonic dystrophy type 1 (DM1).

Photo: David Altshuler, executive vice president of global research, and chief scientific officer of Vertex

Myotonic dystrophy type 1 (DM1) is an underrecognized, progressive and often fatal disease caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. The disease is highly variable with respect to severity, presentation, and age of onset, however all forms of DM1 are associated with high levels of disease burden and may cause premature mortality. DM1 primarily affects skeletal and cardiac muscle, but patients can also suffer from a constellation of manifestations including myotonia and muscle weakness, respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment. Currently, there are no treatments for patients living with DM1, which affects an estimated 40,000 people in the United States.

The collaboration includes Entrada’s program for DM1, ENTR-701, which is in late-stage preclinical development. ENTR-701 is a proprietary Endosomal Escape Vehicle (EEV)-conjugated phosphorodiamidate morpholino oligomer, and the second novel clinical candidate from Entrada’s growing pipeline of EEV therapeutics. ENTR-701 is designed to address the underlying cause of myotonic dystrophy type 1 through allele-specific targeting of the disease-associated trinucleotide repeats in dystrophia myotonica protein kinase transcripts. In doing so, ENTR-701 has the potential to restore the function of muscle blind-like proteins, correct the mis-splicing and aberrant expression of downstream transcripts and restore normal muscle function. Data from preclinical studies of ENTR-701 suggest correction of disease relevant biomarkers in various muscle groups.

“Our collaboration with Vertex represents an important step for Entrada as we work to make intracellular therapeutics a reality through our novel EEV approach,” said Dipal Doshi, president and CEO of Entrada Therapeutics. “DM1 is a progressive disease with no treatment options available. Working with Vertex will enable us to expeditiously move this program forward, while focusing the majority of our internal resources on advancing new therapeutic options for patients living with Duchenne and expanding our commitment to non-neuromuscular disease programs.”

Under the terms of the agreement, Entrada will receive an upfront payment of $224 million, as well as an equity investment of $26 million. Entrada is eligible to receive up to $485 million for the successful achievement of certain research, development, regulatory and commercial milestones, and tiered royalties on future net sales for any products that may result from this collaboration agreement.

The agreement includes a four-year global research collaboration whereby Entrada will continue to advance and receive payments for certain research activities related to ENTR-701, as well as additional DM1-related research activities. Vertex will be responsible for global development, manufacturing, and commercialization of ENTR-701 and any additional programs stemming from Entrada’s DM1 research efforts.

“Vertex’s strategy is to discover and develop transformative medicines for people with serious diseases, and DM1 has therefore been a disease area of interest to Vertex for some time,” said David Altshuler, executive vice president of global research, and chief scientific officer of Vertex. “Entrada’s innovative EEV approach, the significant progress in their DM1 program, and the potential for it to reach the clinic in the near-term hold exciting potential for patients.”

Author: Rare Daily Staff