I am excited to report on impressive progress in the development of Odylia Therapeutics’ emerging gene therapy for retinal degeneration caused by RPGRIP1 mutations, which is most often diagnosed as LCA6. Like the journey for so many inherited retinal disease treatments and the companies that develop them, there’s a long story here ⎯ a story of commitment, resourcefulness, and persistence. I’ll touch on that in a moment, but I encourage you to learn much more from an enlightening Hope in Focus podcast interview I conducted with Ashley Winslow, PhD, chief executive officer at Odylia, on March 3rd. It’s an excellent episode, if I do say so myself.

Background on RPGRIP1-associated disease

The RPGRIP1 protein is critical for the structural development of photoreceptors (rods and cones) and the trafficking of important proteins. Remember, photoreceptor cells are long, thin, light-sensing cells in the retina that enable us to see, and many different proteins need to move up the length of the cells for them to work properly and survive long term. That movement is called trafficking. 

Also, remember that genes are like recipes for proteins. Cells read genetic messages to make proteins, and ultimately, it’s the proteins that are critical to our cells’ function and survival. In the LCA6 case, if there are spelling mistakes (i.e., mutations) in the RPGRIP1 gene, there isn’t sufficient RPGRIP1 protein produced, and photoreceptors suffer.

Mutations in the RPGRIP1 gene cause LCA6 but can also be associated with milder forms of retinal disease, such as cone-rod dystrophy (CORD), retinitis pigmentosa, or achromatopsia. Though LCA6 usually causes significant vision impairment at birth, photoreceptors can potentially survive into young adulthood, thereby providing a wide treatment window for patients.

The RPGRIP1 gene therapy story

Initial development of Odylia’s gene therapy began at Mass Eye and Ear (Harvard) more than 15 years ago. Researchers there demonstrated efficacy for gene therapy in mouse models. With sustained funding from Odylia, the RPGRIP1 gene therapy has moved into a safety and toxicology study, a critical step before moving into a clinical trial. The study will also help researchers determine the optimal dosing range for the trial. Also important, Odylia has clinical manufacturing in place and received positive feedback from the FDA on the trial design. However, additional funding is needed to launch the trial.

Odylia also has gene therapy programs underway for vision loss due to mutations in the USH1C and NPHP1 genes, which are in preclinical development.

The Odylia story

Odylia was formed in 2017 as a nonprofit collaboration between Scott Dorfman, a father of two children with Usher syndrome 1C, and gene-therapy pioneer Luk Vandenberghe, PhD, of Mass Eye and Ear. Their goal: Provide the commitment and resources needed to advance rare disease treatments into early-stage clinical trials. In the podcast, Ashley Winslow, PhD, Odylia’s chief executive officer, said that as a nonprofit, Odylia has a stronger commitment to rare disease therapy development than a typical for-profit biotech or pharmaceutical company that’s focused on minimizing financial risk and maximizing revenue. By de-risking therapies through early-stage development, Odylia aims to attract investment partners (i.e., for-profits) to its programs.

Dr. Winslow explained that the key to Odylia’s success is its collaboration with patient groups, academic researchers, manufacturers, and clinical research organizations to find a way forward both in fundraising and therapy development. “In the rare disease space, you have to think about the science and the fundraising hand in hand because financial resources are often limited,” she said. 

If you’re interested in learning more about Odylia and its emerging therapies, you can reach out to Dr. Winslow at awinslow@odylia.org.

And make sure you check out the Odylia episode on the Hope in Focus podcast, available on all streaming platforms.