Phase I trial for ISTH0036 advanced glaucoma treatment

Isarna Therapeutics has begun a Phase I clinical trial of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta (TGF-ß2), to treat advanced glaucoma.

The trial will evaluate the safety and long-term tolerability of ISTH0036 in 24 to 30 patients who have advanced glaucoma and are undergoing trabeculectomy due to uncontrollable elevated IOP. They will be treated with escalating doses of ISTH0036 and also will be monitored for IOP and visual field preservation.

“ISTH0036, with its expected three-directional activity, which includes blocking TGF-ß2-mediated trabecular meshwork alteration and inhibiting both direct optic nerve toxicity and scarring post trabeculectomy, has the potential to substantially alter the course of this disease and protect the patient’s vision,” Prof. Eugen Leo, Isarna’s head of clinical development, said in a statement. “Notably, ISTH0036 is currently the sole compound in clinical development worldwide that directly targets the core driver of the pathophysiology of glaucoma: TGF-ß2,” he added.

TGF-ß plays an important role in key pathways such as cell proliferation, cell differentiation, immune response and tissue modeling. Significantly elevated levels of TGF-ß have been identified in glaucomatous eyes in the anterior chamber, the vitreous, and optic nerve head. TGF-ß has been shown to directly cause increased IOP, a critical risk factor in the progression of glaucoma through complex interaction with the trabecular meshwork, leading to decreased aqueous humour outflow and has been linked to direct optic nerve toxicity.

Preclinical studies, according to Isarna, have demonstrated that ISTH0036 is highly potent and shows selective target engagement (TGF-ß2 mRNA and protein downregulation) consistent with long-lasting tissue uptake and pharmacodynamic effects.

The trial is being conducted at the University Hospitals of Mainz and Tuebingen, Germany. Isarna is headquartered in Germany and is registered as a Dutch BV as well as a U.S. corporation.