BioLineRx Successfully Completes Phase 1 Clinical Trials of BL-1020, First in Class GABA-Enhanced Antipsychotic for the Treatment of Schizophrenia

JERUSALEM--(BUSINESS WIRE)--Feb 13, 2007 - Speaking today at the BIO CEO & Investor Conference 2007, Morris C. Laster, MD, CEO of BioLineRx Ltd. (TASE: BLRX), Israel's leading drug development company, announced the successful completion of Phase 1 clinical trials of its most advanced drug, BL-1020, the first GABA enhanced antipsychotic for the treatment of schizophrenia. The study results showed that BL-1020 was well tolerated and showed an improved safety profile reducing extrapyramidal symptoms that are experienced with currently available therapies.

"The current generation of anti-schizophrenia drugs is effective in less than 60% of the patients who suffer from schizophrenia, and even in these patients, it produces adverse effects that cause the patients to discontinue medication. More effective and better tolerated drugs are urgently needed," commented Professor Michael Davidson, Director Department of Psychiatry, Sheba Medical Center." Results from the Phase I trial indicate that BL-1020 might be better tolerated than currently available drugs. In addition BL-1020 is the only antipsychotic with the potential to increase the activity of the neurotransmitter GABA which appears to be deficient in schizophrenia. Increased GABA activity might also reduce anxiety and improve cognitive function in patients suffering from schizophrenia."


"We are very encouraged by the results of these Phase 1 studies," Morris C. Laster, MD, CEO of BioLineRx stated. "These results support our belief that BL-1020 holds great potential as a next generation antipsychotic which will increase patient compliance. We are looking forward to the initiation of Phase 2 studies expected to begin later this year."
About the trial

The Phase 1 trial of BL-1020 was a randomized, double blind, placebo-controlled, dose-escalation, single center study in healthy adult males (ages 21-45). The primary objective was to evaluate the safety and tolerability of escalating doses of BL-1020. The secondary objectives were to determine the pharmacokinetics of BL-1020, and to assess its ability to block activity of the neurotransmitter dopamine, implicated in schizophrenia.

A total of 48 volunteers were randomized and enrolled into 6 dose cohorts at a ratio of 6:2 (BL-1020 : placebo). In each cohort, patients received a single dose or matching placebo (4, 8, 16, 24, 32 or 40 mg). The results demonstrate that BL-1020 was well tolerated following administration of a single dose up to 40 mg, with no adverse drug related effects on ECG parameters, clinical lab data and neurological assessments.

Clinical activity of BL-1020 was assessed by its ability to antagonize dopamine activity. Dopamine hyperactivity is implicated in schizophrenia, and various antipsychotic drugs work by blocking dopamine activity. The effect of BL-1020 on dopamine levels was assessed by monitoring serum prolactin, a surrogate marker for dopamine antagonism. The pharmacokinetics of BL-1020 were linear across the range of doses studied, as assessed by the dose-dependent elevation of serum prolactin levels.
Currently available drugs, which also reduce dopamine activity, induce significant clinical side effects, thereby limiting patient compliance. The results are that BL-1020 is protective against extrapyramidal symptoms (EPS). In addition to dopamine hyperactivity, schizophrenia is also associated with hypo-activity of the neurotransmitter GABA, and BL-1020 also acts as a GABA enhancer by delivering GABA to the CNS.

About Schizophrenia
Schizophrenia is a serious mental disorder that affects about 1% of the world's population. It is a multifactorial disease characterized by delusions and hallucinations, emotional withdrawal and apathy, poor attention and disorganization. In 2002, the overall cost of schizophrenia in the United States was estimated at $62.7 billion, and the market for schizophrenia therapy in the U.S. is estimated to reach approximately $10 billion in 2012.

About BL-1020
BL-1020 is an orally available GABA enhanced antipsychotic for the treatment of schizophrenia that was shown in preclinical studies to retain the efficacy of currently available typical and atypical antipsychotic drugs while achieving a much higher safety profile as evidenced by a lack of metabolic or extrapyramidal side effects.

BL-1020 is designed to simultaneously target the dopamine hyperactivity and GABA hypoactivity of schizophrenia. Exogenously administered GABA is ineffective as a therapeutic agent due to its inability to cross the blood brain barrier. Pharmacokinetic studies demonstrate that BL-1020 provides effective transport of GABA into the brain, overcoming this challenge. Receptor binding studies indicate that BL-1020 has a high affinity to dopamine and specific GABA-A agonist activity. This unique clinical profile may explain the reduction in side effects observed in animals and may contribute to improving cognitive function in schizophrenia.

BL-1020 is being developed by BioLineRx, Ltd. under a worldwide exclusive license from Ramot at Tel Aviv University Ltd. and Bar-Ilan Research and Development Company Ltd., the technology transfer arms of Tel Aviv University and Bar-Ilan University respectively. BL-1020 was discovered by Professor Abraham Nudelman from the Department of Chemistry, Bar-Ilan University; and Ada Rephaeli, Ph.D., Professor Abraham Weizman, MD, and Irit Gil-Ad, Ph.D. from the Sackler Faculty of Medicine, Tel Aviv University