ESR10: Optimisation, delivery and tolerability of antisense oligonucleotides to treat STGD1 patients with the most common splice mutations in ABCA4
Abstract
ProQR is currently in Phase IIa clinical development with a splice modulating AON (QR-110) targeting the deep-intronic c.2991+1655A>G mutation in LCA type 10. In addition, they have two additional AON programs in Usher syndrome targeted all exon-13 mutations (QR-421a) and c.7595-2144A>G (QR-411a), respectively, in pre-IND/CTA enabling studies. ProQR is also in the discovery phase with regards to an intronic ABCA4 mutation (c.5461-10T>C), one of the most frequent mutations underlying STGD1 that results in the exclusion of exon 39, or exon 39 and exon 40 together, from the mRNA, leading to a frameshift. ESR10 will continue this program and optimise the sequence and chemistry of the final molecule to generate a clinical development candidate. This lead candidate will be further optimised by determining the extent of target engagement using digital-droplet PCR, immune-profiling against human donor T-lymphocyte panels, delivery to photoreceptors tolerability and pharmacokinetic parameters following intravitreal injection of mouse and rabbit models.
Partner
ProQR Therapeutics, Leiden, The Netherlands (www.proqr.com)
Supervisor
Prof. Dr. P. Adamson
ProQR is currently in Phase IIa clinical development with a splice modulating AON (QR-110) targeting the deep-intronic c.2991+1655A>G mutation in LCA type 10. In addition, they have two additional AON programs in Usher syndrome targeted all exon-13 mutations (QR-421a) and c.7595-2144A>G (QR-411a), respectively, in pre-IND/CTA enabling studies. ProQR is also in the discovery phase with regards to an intronic ABCA4 mutation (c.5461-10T>C), one of the most frequent mutations underlying STGD1 that results in the exclusion of exon 39, or exon 39 and exon 40 together, from the mRNA, leading to a frameshift. ESR10 will continue this program and optimise the sequence and chemistry of the final molecule to generate a clinical development candidate. This lead candidate will be further optimised by determining the extent of target engagement using digital-droplet PCR, immune-profiling against human donor T-lymphocyte panels, delivery to photoreceptors tolerability and pharmacokinetic parameters following intravitreal injection of mouse and rabbit models.
Partner
ProQR Therapeutics, Leiden, The Netherlands (www.proqr.com)
Supervisor
Prof. Dr. P. Adamson
