Ester Neurosciences Starts Oral Antisense Extension Study for Myasthenia Gravis.

Business Editors/Health/Medical Writers

HERZLIYA, Israel--(BUSINESS WIRE)--June 16, 2003

Ester Neurosciences announced today that it has begun a second Phase Ib trial using EN101, the company's novel antisense drug for the treatment of myasthenia gravis. The new trial is an extension study of a previous Phase Ib trial conducted earlier this year.

"The new study will provide more information about the long-term efficacy of EN101 in the treatment of myasthenia gravis," said Dr. Eli Hazum, CEO of Ester Neurosciences. In the new trial, patients receive the drug for a period of 30 days compared with four days in the previous study. Myasthenia gravis (MG) is a chronic and debilitating disease characterized by muscle weakness that affects about 15 persons per 100,000.

The complete results of the successful initial Phase Ib trial are being presented on June 17 at a meeting of the European Neurological Society in Istanbul, Turkey, by Dr. David McKee, a clinical Research Fellow, and Dr. Jon Sussman, a neurologist, both working at the Greater Manchester Neuroscience Centre in the U.K.

This breakthrough study demonstrated for the first time effective and safe use of an orally-administered antisense therapy for a neurological condition.

Dr. Jon Sussman, a leading expert in the treatment of myasthenia gravis and lead Investigator at the U.K. trial site, commented: "We were very impressed with the striking improvement in the condition of our patients. EN101 even enabled some patients with limited mobility to regain their ability to stand and walk without assistance."

EN101 is the lead compound in Ester's disease-modifying platform technology for the pre-expression control of a specific variant of the AChE protein, which is applicable to a wide range of neurological disorders. "The results of the study suggest that our platform technology may have wide applications in muscle fatigue syndromes and co-morbidities as well as in the treatment of many other CNS disorders such as Alzheimer's Disease and traumatic brain injury," said Dr. Eli Hazum, CEO of Ester Neurosciences.

The technology is based on balancing cholinergic transmission via controlled modulation of the company's novel target, a stress-response variant of acetylcholinesterase (AChE). AChE is an enzyme that degrades the neurotransmitter acetylcholine. EN101 selectively inhibits the production of the target at the critical stage of its biosynthesis, thereby allowing an effective treatment, while minimizing side effects and substantially improving upon the short-duration palliative relief currently observed with conventional inhibitors.

Oral delivery is a critical attribute that has been long sought after by antisense drug developers. Oral delivery is expected to improve patient compliance as it eliminates the need for daily or more frequent injections.

About Ester Neurosciences:

Ester Neurosciences Ltd. is a clinical stage biotechnology company that is committed to the discovery and development of novel therapeutic products for the treatment of neurological disorders. Ester's lead product in development, EN101, was successfully tested against MG in a sixteen-patient Phase Ib trial, in which oral administration of EN101 in a liquid format resulted in marked improvement in MG symptom severity, with no cholinergic symptoms nor significant adverse events. Fourteen out of sixteen patients had better scores on the Quantitative Myasthenia Gravis (QMG) scale on the last day of dosing compared to the initial baseline. Improvements of total QMG for these days ranged from 27.8% to 53.4% (p less than 0.01). The Phase Ib trial results showed that EN101 appears to have superior efficacy, longer duration of action and a more favorable side effects profile than currently used medications. The results of the MG trials appear to provide proof of principle for the novel and proprietary mechanism of action discovered through Ester's pioneering research on the enzyme acetylcholinesterase, which mechanism may potentially lead to the discovery of new medications for Alzheimer's disease and other disorders of the central nervous system.

About myasthenia gravis (MG):

MG is a chronic, debilitating disease characterized by fatigable weakness of muscles which affects about 15 persons per 100,000. Symptoms include double vision, drooping eyelids, difficulty chewing, swallowing, smiling and speaking, weakness of arms and legs, and breathlessness. MG is usually progressive, often crippling and sometimes fatal when the muscles of breathing and swallowing are involved. Current treatments are only modestly effective and carry risks and side effects. MG results from an autoimmune attack against receptors for the neurotransmitter acetylcholine at the neuromuscular junction, which interference disrupts nerve-to-muscle signaling. MG may develop at any age from one year onwards, and spontaneous recovery is rare.

For more information visit www.esterneuro.com or contact:

Eli Hazum, Ph.D

Ester Neurosciences

11 Hamanofim Street

Herzlia Pituach, Israel

Tel: [phone]

Fax: [phone]

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