BioWorld International Correspondent

ZICHRON YA'AKOV, Israel - Ester Neuroscience said EN101, an oral antisense oligonucleotide for myasthenia gravis, provided clear symptomatic improvement in a Phase Ib trial.

"These significant positive results occurred without any adverse events," said the study's principal investigator, Zohar Argov, as the announcement was made by Ester last week in Honolulu at a session of the American Academy of Neurology meeting.

EN101 is Ester's lead compound in its disease-modifying platform technology for the pre-expression control of a specific variant of the AChE protein. EN101 is a 20-mere oligonucleotide with a sequence complementary to a coding region in the human acetylcholinesterase (AChE) gene. Earlier studies forged by team leader Hermona Soreq, head of life sciences at the Hebrew University of Jerusalem, showed it prevented AChE translation.

More recently, another leader in the Israeli group, Talma Brenner, in the neurology department of the Hadassah University Hospital in Jerusalem, told BioWorld International the antisense drug was shown to suppress AChE production while also reversing symptoms and signs in rats with experimental autoimmune MG.

Argov noted "significant and marked behavioral improvement during and following the study period by continuous decrease in QMG [quantitative MG score]." Specifically, 15 of 16 patients with stable generalized MG who had required constant AChE inhibitors (pyridostigmine) for daily functioning were weaned in the hospital from pyridostigmine and given EN101 in escalating oral doses during the first day, followed by a daily dose of 500 g/kg for three days, and during the 72-hour drug washout period (after which pyridostigmine had to be reinstated).

"EN101 appeared to effectively reverse symptoms in patients with stable MG," Argov said.

Neurologist Jon Sussman, lead investigator at the Greater Manchester Neuroscience Centre, a UK trial site, said, "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 to walk without aids."