Opus Genetics receives FDA clearance to advance RDH12-LCA gene therapy into clinical development

“We are pleased to advance our third gene therapy pipeline program into clinical development and plan to initiate a Phase 1/2 trial this quarter. Receiving IND clearance for OPGx-RDH12 represents an important step toward bringing a potentially transformative gene therapy to children and families affected by this devastating disease. We are grateful for the collaboration and commitment of our partners at the Global RDH12 Alliance, which has been instrumental in advancing this program into the clinic.” – George Magrath, M.D., Chief Executive Officer, Opus Genetics.

What is LCA?

Leber Congenital Amaurosis (LCA) is a rare genetic eye disease that appears at birth or in the first few months of life. The extent of vision loss varies between individuals but is generally more rapid and severe than other forms of retinal disease. LCA is actually a term given to a group of diseases that are caused by mutations in at least 25 genes.

RDH12-LCA affects an estimated 30,900 people globally and is caused by mutations in the RDH12 gene. The RDH12 gene contains the instructions needed for making an enzyme called retinol dehydrogenase 12. In healthy eyes, this enzyme helps to process substances involved in the visual cycle and clear potentially harmful chemicals produced when the eye responds to light. When this enzyme is faulty or missing, because the instructions in the RDH12 gene are incorrect, these substances can build up and put stress on the light-sensing photoreceptor cells. Over time, this build up causes the photoreceptors to degenerate and die, causing progressive vision loss.

RDH12-LCA often causes structural retinal changes by the age of two. There are currently no available treatments for RDH12-LCA. However, Opus Genetics have an investigative treatment in development, OPGx-RDH12, which will now begin clinical development.

What is OPGx-RDH12?

OPGx-RDH12 is an investigational adeno-associated virus (AAV)-based gene therapy. This means that a small virus, that doesn’t cause illness in humans, is used as a delivery system to introduce or alter genetic material within cells. The therapy is designed to deliver a functional copy of the RDH12 gene directly to photoreceptor cells in the retina so they can produce the enzyme they need. The hope is to protect these cells and preserve vision.

Preclinical studies of OPGx-RDH12 in cell and mouse models have demonstrated restoration of RDH12 activity and functional improvements, supporting its progression into clinical development.

What does this update mean?

Opus Genetics has announced that the U.S. Food & Drug Administration (FDA) has authorised OPGx-RDH12s progression to a phase 1/2 clinical trial, passing the Investigative New Drug (IND) stage. This advancement into clinical development marks an important but early milestone and hopes to build on the encouraging results seen in preclinical animal model studies.

This work has been achieved through Opus Genetics’ collaboration with the Global RDH12 Alliance. The RDH12 Global Alliance is an international collaboration of charities and patient organisations working together to accelerate research and find treatments for people affected by RDH12-associated inherited retinal disease. Since the partnership with Opus Genetics was formed in July 2025, the Global RDH12 Alliance has committed up to $1.6 million toward the development of OPGx-RDH12. To read more about them, please visit Eyes on the Future, the UK contingent here: Global RDH12 Alliance – Eyes On The Future

“This is what true co-development looks like. Our RDH12 patient organizations and Opus have pooled resources, capabilities and risk to bring this rare gene therapy into the clinic, combining venture philanthropy, scientific innovation and a patient-driven sense of urgency. We have been working toward this moment for many years, and we are grateful to Opus for being a true partner. We believe this model can become a blueprint for bringing gene therapies to rare disease communities, and one that other patient organizations can follow.” – Silvia Cerolini, Chief Executive Officer of Eyes on the Future and mother of a child affected by RDH12-LCA.

Please note that this IND approval is U.S specific and only authorises clinical trial testing to begin. It does not mean the treatment has been approved or is available to patients. The FDA is the regulatory body in the U.S and does not have any authority in the U.K. A regulatory body is an organization that makes sure that medical treatments are safe, effective and of high quality before they can be offered to patients more widely. Examples include the FDA in the U.S and the Medicines and Healthcare products Regulatory Agency (MHRA) in the U.K. Each of these organisations exist because healthcare systems, laws and public safety standards vary from country to country.

Each regulatory body has its own questions, forms and requirements when reviewing research data. That’s why it can take a while for a new treatment to reach regulatory milestones across multiple countries. For the Retina UK community however, it means that every step toward a breakthrough is carefully checked to ensure potential new treatments are both safe and effective. The FDA IND clearance is a positive sign that OPGx-RDH12 can now begin clinical trial testing in humans.

Companies do typically target the FDA first because of the size and value of the U.S market, so the U.K often just needs to wait, even though this is very frustrating.

Opus Genetics reportedly plan to initiate this early stage, phase 1/2 clinical trial during this quarter, although no further information has been released as of yet regarding recruitment timelines or eligibility criteria. We look forward to hearing an update from Opus Genetics soon!

For more information, please visit the Opus Genetics website found here: Opus Genetics