Sepul Bio’s LCA10 RNA Therapy Moves into Phase 3 Clinical Trial

Sepul Bio, a business unit of Laboratories Théa developing RNA therapies for inherited retinal diseases (IRDs), dosed the first participants in the Phase 3 HYPERION clinical trial for sepofarsen, its emerging RNA therapy for individuals with Leber congenital amaurosis 10 (LCA10) caused by the c.2991+1655A>G (IVS26) mutation in the CEP290 gene. The two-year HYPERION trial will enroll a total of 32 patients, including adults and children six years of age or older, at sites in the US, Canada, and Europe. The Foundation’s My Retina Tracker Patient Registry is being used for patient recruitment in the US.

The HYPERION study is double-masked, randomized, and placebo-controlled. At the start of the study, the two eyes of each patient are randomized so that one eye receives sepofarsen and the other eye receives placebo for the first year. Sepofarsen and the placebo will be injected into the vitreous, the soft gel in the middle of the eye, every six months.

In December 2024, Sepul Bio dosed the first patient in the Phase 2b LUNA clinical trial for ultevursen, its emerging RNA therapy for people with retinitis pigmentosa or Usher syndrome caused by mutations in exon 13 of the USH2A gene. The two-year clinical trial will enroll 81 patients (adults and children over eight years of age) at multiple global sites. 

Both sepofarsen and ultevursen are comprised of tiny pieces of genetic material called antisense oligonucleotides (AONs). The AONs mask the disease mutation in RNA, the genetic messages that cells read to make proteins which are critical for the cells’ health and function. Masking the mutation enables cells to make functional protein. AONs can be advantageous when large retinal disease genes — such as CEP290 and USH2A — exceed the capacity of viral gene replacement delivery systems, thereby making gene therapy development for these genes challenging.

In December 2023, Théa acquired ProQR’s ophthalmology assets, which included sepofarsen and ultevursen. Théa launched its Sepul Bio business unit to continue clinical development of ultevursen and sepofarsen, both of which improved vision in earlier clinical trials.

The RD Fund, the Foundation’s venture philanthropy arm, invested in the development of ultevursen when the treatment was initially being developed by ProQR.