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Opus Genetics Inc., has announced the “first-in-patient” in a Phase 1/2 clinical trial for “OPGx-001” for the treatment of LCA5 retinal disease.

Opus Genetics Inc., a private ocular gene therapy company based in Raleigh, North Carolina, has announced its “first-in-patient” in a Phase 1/2 clinical trial for “OPGx-001” for the treatment of LCA5 retinal disease.  This is the first-in-human clinical trial (NCT05616793) of OPGx-001 in patients with Leber congenital amaurosis (LCA) resulting from biallelic mutations in the LCA5 gene (LCA5).  The Phase 1/2, open-label, dose-escalation trial will evaluate the subretinal delivery of OPGx-001 in nine adult patients with LCA5. The objective of the trial is to evaluate safety and potential benefit.


Previously defined as a juvenile form of RP (retinitis pigmentosa), LCA is a severe congenital or early infant-onset form of non-syndromic retinal disease, characterised by severe retinal dystrophy, vision loss, nystagmus, an absence of a normal pupil response and an almost non-recordable ERG.  The clinical diagnosis does not have a well agreed-upon definition and therefore a more recent structure for nomenclature, aiming to define the basis as being on genotype, rather than phenotype.  To date, there are now 25 genes causative for LCA, one of which, Lebercilin (LCA5), now accounts ~ 2% of LCA cases and results in a particularly severe form of the disease. The LCA5 gene located in chromosome 6q14.1 encodes an 80 kDa protein expressed in the connecting cilium of photoreceptors.  


Opus Genetics Inc., stated that 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 animal and human iPSC models, have demonstrated preservation of retinal structure and visual function when OPGx-001 was administered prior to peak disease severity.  Studies in LCA5 patients have reported evidence for the dissociation of retinal architecture and visual function in this disease, suggesting an opportunity for therapeutic intervention through gene augmentation.  Commenting on the milestone, Ben Yerxa, PhD, CEO of Opus, that, “dosing our first patient establishes Opus as a clinical-stage company and is a point of progress in our mission to advance first-in-class gene therapies for inherited retinal diseases. Despite the severe retinal dysfunction in patients with LCA5, preclinical data suggest an opportunity for therapeutic intervention, including retinal structural and functional restoration when OPGx-LCA5 was administered prior to peak disease severity. We look forward to progressing the trial of this potentially transformative therapy for patients affected by LCA5.”