Isarna has established a broad portfolio of next-generation first- and best-in-class antisense oligonucleotides blocking three key TGF-β variants with therapeutic potential across a range of indications. In ophthalmological indications, our compounds are clearly differentiated from the currently marketed anti-VEGF compounds such as Eylea and Lucentis and offer the potential for improved efficacy. Isarnahas started Phase 2a development in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). The approach has near-term upside potential through expanding the program into other key ophthalmology indications i.e., dry forms of age-related macular degeneration.
ISTH0036 is a locked nucleic acid-modified antisense oligonucleotide selectively targeting the messenger RNA (mRNA) of TGF-β2. Preclinical studies have demonstrated that ISTH0036 is highly potent and shows selective target engagement (TGF-β2 mRNA and protein downregulation) consistent with long-lasting tissue uptake and pharmacodynamic effects.
Isarna and its collaboration partners presented Phase I safety and efficacy data in advanced-stage glaucoma patients undergoing trabeculectomy for ISTH0036 at The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in 2017. Overall, the treatment was safe and well tolerated at all dose levels and a trend in post-operative intraocular pressure (IOP) analysis provided preliminary evidence for a beneficial effect of ISTH0036 at the two highest dose levels evaluated.