Pipeline & Programs

Strong and growing portfolio

Opus’ lead programs focus on treatments delivered subretinally to address mutations in genes that cause different forms of Leber congenital amaurosis (LCA).


*Estimated IND filing and first-in-human trials commence


Opus’ first three indications are rare, occurring in hundreds to low thousands of patients in the U.S. and EU. While LCA is a group of rare inherited retinal diseases (IRD) characterized by degeneration of photoreceptors that affect about 1 in 40,000 newborns, LCA5 affects approximately one in 1.7 million people, retinal dystrophy caused by mutations in the RDH12 gene affects one in 288,000 people, and disease caused by mutations in the NMNAT1 gene affects one in 432,000 people in the U.S.

OPGx-001 for LCA5 IRD

Opus’s lead program, OPGx-001, is designed to address mutations in the LCA5 gene, which encodes the lebercilin protein.

LCA5 is an early-onset retinal degeneration with evidence of a structural-functional dissociation, which suggests a therapeutic opportunity to target the mutation. OPGx-001 utilizes an adeno-associated virus 8 (AAV8) vector to precisely deliver a functional LCA5 gene to photoreceptors in the retina. Preclinical data, including faithful animal and human iPSC models, have demonstrated preservation of visual function when OPGx-001 was administered prior to peak disease severity, indicating the potential for a broad therapeutic window for patients with LCA5.

Opus expects to file an IND for its OPGx-001 program in early 2022 and enter the clinic in mid-2022.

Eye structure showing detail of rods and cones in normal and diseased states

LCA5 is a severe, early-onset form of IRDs. The LCA5 gene encodes for the protein lebercilin, a ciliary protein which is critical for bidirectional protein trafficking in the inner and outer photoreceptor segments, which are responsible for absorbing light and transducing this signal in order to enable vision. In LCA5, the outer segments do not properly develop and photoreceptor function is severely impaired.

OPGx-002 for RDH12 IRD

The company’s second program, OPGx-002, will focus on restoring protein expression and halting functional deterioration in patients with retinal dystrophy caused by mutations in the retinal dehydrogenase (RDH12) gene.

Patients with RDH12 mutations often have early visual acuity loss with retinal structural changes by 2 years of age, and longitudinal studies have reported a steep decline in visual acuity within the second decade of life. OPGx-002 also leverages an AAV8 vector, transporting a functional gene to photoreceptors in the retina. Preclinical studies of OPGx-002 in cellular and mouse models have demonstrated functional improvement and efficacy, including the restoration of RDH12 activity to approaching wild type levels in mice with mutations in the RDH12 gene.
Opus anticipates an IND in the next 12-18 months.

Illustration showing blowup of rods and cones and the role of RDH12 in signaling

RDH12 is another severe early-onset IRD. The RDH12 gene encodes for an enzyme, a type of retinol dehydrogenase in the photoreceptor inner segment, which is responsible for serving as a key reductase in the visual cycle. RDH12 also plays a key role in protecting photoreceptors from cytotoxicity associated with products that are generated during the visual cycle. Mutations in RDH12 cause photoreceptor cell loss due to buildup of excess toxins.

OPGx-003 for NMNAT1 IRD

OPGx-003 is a gene augmentation therapy designed to halt functional deterioration in pediatric patients with retinal degenerative disease caused by mutations in the nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) gene.

NMNAT1 is an enzyme essential for regeneration of nicotinamide adenine dinucleotide (NAD+) retinal pools, which govern essential cellular processes. Photoreceptors, in particular, are highly vulnerable to loss of NMNAT1 function. OPGx-003 uses NMNAT1 gene therapy for structural rescue of retinal tissue. Preclinical data in mouse models exhibiting pathogenic features of human NMNAT1-inherited retinal degeneration have demonstrated the potential for OPGx-003 to achieve stable rescue of retinal structure and function.

Opus anticipates an IND in 2024.