Germany-based Isarna Therapeutics has started the first-in-human Phase I clinical trial with ISTH0036, an antisense oligonucleotide selectively targeting TGF-ß2, for the treatment of advanced glaucoma.
Conducted at the University Hospitals of Mainz and Tuebingen in Germany, the trial will evaluate the safety and long-term tolerability of ISTH0036 in patients with advanced glaucoma undergoing filtration surgery (trabeculectomy) due to uncontrollable elevated intraocular pressure (IOP).
Around 24-30 patients will be enrolled in the trial and they will be treated with escalating doses of ISTH0036.
Apart from the safety, patients will be monitored for intraocular pressure and visual field preservation.
Isarna head of Clinical Development professor Eugen Leo said: "Glaucoma is the leading cause of irreversible blindness in the world, and 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.
"Notably, ISTH0036 is currently the sole compound in clinical development worldwide that directly targets the core driver of the pathophysiology of glaucoma: TGF-ß2."
TGF-ß plays a major role in key pathways such as cell proliferation, cell differentiation, immune response and tissue modelling, while significantly elevated levels of TGF-ß have been observed in glaucomatous eyes in the anterior chamber, the vitreous and optic nerve head.
University College London/Moorfields Eye Hospital professor of Glaucoma and Ocular Healing and clinical advisor to Isarna Peng Khaw said: "This novel oligonucleotide selectively targeting TGF-ß2, an important driver of glaucoma, seems to possess impressive PK-PD properties that could make it a valuable treatment for different aspects of glaucoma."
According to the company, TGF-ß has been shown to directly cause increased intraocular pressure leading to decreased aqueous humor outflow and has been linked to direct optic nerve toxicity.
Isarna Therapeutics CEO Dr Philippe Calais said: "The start of our first Phase I trial in advanced glaucoma is a major corporate milestone, one that we have achieved two years after starting this program thanks to an outstanding and expedited preclinical program.
"We are excited to move this and other compounds forward to successfully treat glaucoma and other major ophthalmic diseases."
Image: Acute angle closure glaucoma of the right eye. Photo: courtesy of James Heilman, MD.