ARVO 2024 Highlight: PYC Reports Initial Clinical Trial Results for its RNA Therapy Targeting RP (PRPF31 Mutations)
Eye On the Cure Research News
No serious adverse events were reported. One patient had encouraging improvement in retinal sensitivity.
PYC Therapeutics, an Australia-based developer of RNA therapies, reported initial results from its Phase 1 PLATYPUS clinical trial in the US for an RNA therapy known as VP-001 for people with retinitis pigmentosa 11 (RP11) which is caused by mutations in the gene PRPF31. The report was delivered by Fred Chen, MBBS, PhD, associate professor, Lions Eye Institute, at the 2024 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), May 5-9, in Seattle.
A total of nine patients — three patients in three dosing groups (3, 10, and 30 μg) — have been dosed thus far. No serious adverse events were observed. One patient in the 30 μg group had improvement in retinal sensitivity as measured by microperimetry, a test that captures changes in retinal sensitivity at several locations (loci) in the macular (central) region of the retina. The improvement for the treated eye of the patient was greater than 7 dB at 6 loci, which is considered by the US Food and Drug Administration (FDA) to be clinically meaningful.
PYC has filed a trial protocol amendment with the FDA to deliver a dose of 75 μg to a fourth group of patients with less advanced disease.
PYC’s emerging therapy is designed to modify RNA, the genetic messages that cells read to make the proteins which are critical to the health and function of all the cells in the body. By modifying RNA, protein expression can be boosted or reduced, depending on the therapeutic need.
In people with RP11, one copy of their PRPF31 gene is normal and producing a relatively normal level of protein while the other PRPF31 copy is mutated and not producing sufficient protein. The overall reduced level of PRPF31 protein for RP11 patients leads to retinal degeneration and vision loss.
Researchers from PYC found that by downregulating the activity of a different gene, CNOT3, they could boost PRPF31 protein expression. So, they developed VP-001, a tiny piece of synthetic genetic material designed to decrease the amount of RNA expressed by the gene CNOT3, thereby increasing PRPF31 protein expression.
