About Duchenne Treatments In The Pipeline Exon Skipping And Stop Codon Read-Through The DMD gene is made up of 79 pieces called exons. The exons link together to form a code that is read in the cells so that the protein dystrophin can be made. If there is a mutation or fault in the gene the exons no longer fit together and are not readable. The consequence is that very little or no dystrophin is made. Exon skipping drugs hide or ‘patch’ the missing piece so that the exons fit together again and can be read. A functional, although shorter, dystrophin protein is made. Exon skipping has been shown to work in both the mdx mouse and dog models for Duchenne. As the exon skipping drug is designed to skip over a particular exon, different versions need to be made depending on which exons needs to be skipped. The most common mutation is around exon 51 and accounts for approximately 13% of cases of Duchenne. Clinical stage In development Sarepta therapeutics Wave Life Sciences EXONDYS 51 (Eteplirsen) Exon skipping therapy for DMD patients amenable to exon 51 skipping. Eteplirsen is currently undergoing a phase 2 clinical trial with 40 male participants ages 4 to 6. Sarepta are also currently recruiting for a Phase 2 study in 12 male patients ages 6 months to 4 years, who have genotypically confirmed DMD with a deletion mutation amenable to exon 51 skipping. In addition to exon 51 therapy, Wave is investigating therapies targeting exons 45, 53 and 44. Wave announced clinical trials for DMD therapy targeting exon 53 are expected to start in early 2019. Wave Life Sciences WVE-210201 Exon 51 skipping investigational therapy in phase 1 trial. Recruiting up to 40 ambulatory and non-ambulatory males between ages 5 and 18. Data from the trial are expected in Q3 of 2018. Nippon Shinyaku NS-065/NCNP-01 Exon skipping therapy for DMD patients amenable to exon 53 skipping. First patients were dosed in phase 2 clinical trial in January 2017. An open-label extension study of this phase 2 trial is currently enrolling by invitation. This study has an estimated enrolment of 16 male participants between ages 4 and 10. This is taking place across 6 sites in the US. Stop Codon Read-Through Another type of mutation in the DMD gene is called a nonsense mutation or premature stop codon. This type of mutation causes cells to stop synthesizing the protein dystrophin before the process is complete. This leads to a short, non-functional dystrophin protein. Ataluren or Translarna™ is a so called stop codon read-through drug, produced by the pharmaceutical company PTC therapeutics, that has the potential to overcome nonsense mutations in the DMD gene. Ataluren is licensed in the EU for Duchenne and is an investigational product in other jurisdictions. Ataluren is an orally administered small molecule compound. Clinical stage PTC Therapeutics Ataluren (or Translarna) Ataluren is an investigational drug which has the potential to overcome the effects of a nonsense mutation. This stop codon read through drug is licenced in the EU (sold as Translarna) and is an investigational product in other jurisdictions. Translana (ataluren) is currently undergoing a post-approval safety study (PASS) as requested by the European Medicines Agency (EMA). This study is following 200 participants over 5 years who are taking Translana. Phase 3 trials for ataluren are taking place in across centres across the world, including the UK. This study has recruited 219 male participants ages 7-18. The study will take place over 96 weeks to determine the long-term safety of ataluren in boys with nonsense mutation dystrophinopathy.