Gene Signal publishes phase I data on GS-101 for diseases of the eye

Gene Signal, a company focused on developing innovative drugs to manage angiogenesis based conditions, has announced publication of data from a phase I study demonstrating that the antisense oligonucleotide GS-101 (eye drops) is safe, with no signs of intolerability following administration to healthy volunteers.

GS-101 is an antisense oligonucleotide that acts by blocking the production of insulin receptor substrate 1 (IRS-1), a protein required for the formation and growth of new blood vessels. The data were published in the August 2009 issue of the British Journal of Clinical Pharmacology (Vol. 68 (2) pp169-173) by researchers led by Dr. Hermann Kain, University Hospital Basel, Basle, Switzerland.

“This publication describes the excellent safety data we obtained from our first-in-man study with GS-101,” noted Eric Viaud, CEO of Gene Signal. “We have moved GS-101 through clinical evaluation and are now conducting an international phase III trial for the prevention of pathologic corneal neovascularisation, a major risk factor in corneal graft rejection, the most common transplantation procedure that saves the sight of approximately 46,000 people worldwide each year.”

Study Data

The phase I open-label study was designed to investigate the safety, tolerability and bioavailability of GS-101 (eye drops) in 14 healthy volunteers. Initially, one single low dose of GS-101 was administered into one eye. If no signs of intolerance were observed, subjects then received escalating doses of GS-101 (3 times daily) in one eye for 14 days. GS-101 was found to be safe and well tolerated by all 14 subjects in escalating doses (43 to 430 µg/day).

About Corneal Grafts and GS101

Every year, approximately 46,000 corneal grafts are performed worldwide to cure or prevent blindness making this procedure the most frequently performed transplant surgery. However, the 5 year failure rate for corneal grafts is currently around 35%. As with many other graft procedures, donor grafts are always in limited supply, with waiting times for the procedure ranging from 6 months to 2 years. One of the main reasons for graft failure is the natural immune response of the body.

Normally, the cornea is avascular, or deprived of blood and lymphatic vessels, protecting the donor cornea from being rejected. However, under certain circumstances, abnormal new blood vessel creation or neovascularisation occurs, inducing an immune response against the donor graft that can lead to immunological corneal graft rejection.

As currently there is no therapy available, Gene Signal is working on new ways to prevent this syndrome. With GS-101, its antisense oligonucleotide approach, which benefits from orphan designation in Europe, the company aims to block the pathways leading to the formation of blood vessels in the cornea. This approach uses short DNA fragments that specifically target and block the production of IRS-1, a protein required for the formation and growth of new blood vessels.