BioLine is currently conducting an additional clinical trial focusing on cognitive function in schizophrenia. The phase II/III CLARITY trial is designed as a randomized, double-blind clinical trial to examine both acute (6 weeks) and long-term (6 months) antipsychotic and cognitive efficacy, safety and tolerability of BL-1020. It will be conducted at 14 sites in Romania and 18 sites in India on a total of up to 450 patients experiencing an acute exacerbation of schizophrenia. Risperidone, an approved and widely used schizophrenia drug, serves as the positive control for antipsychotic efficacy. The cognition primary endpoint measure will utilize the MATRICS Cognitive Consensus Battery (MCCB), and cognitive benefit will be assessed by comparing the change from baseline in total MCCB score, comparing BL-1020 to Risperidone at the landmarks of six, 12 and 24 weeks.

BL-1020 Phase IIb Clinical Data
BL-1020 has completed a 6-week, double blind, placebo and active control Phase IIb trial. The EAGLE (Effective Anti-psychosis via GABA Level Enhancement) trial was conducted under a U.S. FDA Investigational New Drug (IND) at 40 sites in the USA, Europe and India and involved 363 patients experiencing acute exacerbation of schizophrenia. The patients were randomized to treatment with low (10mg/day) or high (20-30mg/day) dose of BL-1020, Risperidone (2-8mg/day) or placebo.

Trial results demonstrated statistically significant superior efficacy of BL-1020 (20-30mg/day) on the primary study efficacy end-point as well as on the key efficacy measures as compared to placebo.

The primary efficacy measure in the EAGLE study was improvement from baseline of the total PANSS (Positive and Negative Symptom Scale) score. The results show that the BL-1020 high dose group (20-30mg/day) induced a statistically significant reduction in PANSS versus placebo (LS mean -23.6 vs. -14.4; p=0.002).
The superiority of BL-1020 (20-30mg/day) over placebo was also supported by additional secondary efficacy measures such as CGI-S and CGI-C. Furthermore, statistically significant increases in the number of patients rated as ‘responders’ in the BL-1020 (20-30mg/day) group as compared to placebo on the PANSS, CGI-S, and CGI-C, was in line with all other efficacy measures.

Analysis of safety did not indicate any increased toxicity associated with BL-1020 treatment. The incidence of SAEs (Severe Adverse Events) was low in the BL-1020 (20-30mg/day) group (0%) compared to Risperidone (3.3%) and placebo (6.5%). Discontinuations due to AEs (Adverse Events) were similar in the BL-1020 (20-30mg/day) group and in the placebo group (4.3%) but higher in the Risperidone group (8.8%). There were no statistically significant or clinically relevant AEs of body weight gain, glucose increases, and changes in lipids, all indicating that BL-1020 has no metabolic AE propensity. BL-1020 at its high dose level induced a slight increase in the Extra-Pyramidal Symptoms Rating Scale (ESRS) that did not differ significantly from Risperidone (a second generation antipsychotic). The incidence of cardiovascular, sexual, psychiatric, autonomic and gastrointestinal AEs was low and not increased compared to placebo. There were no statistically significant or clinically relevant changes in the measurements of the ECG, laboratory or vital signs (BP, HR. Temp).

The EAGLE trial results also show that BL-1020 improves cognitive function in schizophrenia patients.

Cognitive function in the EAGLE trial was measured by the "Brief Assessment of Cognition in Schizophrenia” (BACS). The BACS test comprises the following six components: verbal memory, digit sequencing, token motor task, verbal fluency, symbol coding and the "Tower of London” puzzle.

Trial results indicate that patients treated with the 20-30mg dose of BL-1020 exhibited a clinically relevant and statistically significant improvement of 9.27 points in the BACS composite score as compared to the placebo group (6.01 points) and the Risperidone group (6.2 points). BL-1020 exhibited statistical significance to both the placebo and Risperidone control groups (p=0.027 for both) with a 0.5 effect size (considered clinically relevant).

In addition, recent results from a recently completed extension trial show patients receiving BL-1020 (20-30mg/day) for 6 additional weeks maintained the improvements in PANSS and CGI (widely recognized measures of severity and improvement in schizophrenia) after 6 weeks of treatment and, more importantly, showed an additional improvement in cognitive function as assessed by BACS. The 12-week treatment was not associated with any increased toxicities - there were no clinically relevant changes in the measurements of the ECG, laboratory or vital signs (BP, HR, Temp). In addition, patients treated with 20-30mg/day BL-1020 showed either no change or a reduction in their Extra-Pyramidal Symptoms Rating Scale (ESRS).

Preclinical and Previous Clinical Results
BL-1020 demonstrated high efficacy in animal models of schizophrenia without the debilitating movement disorders (catalepsy) seen with typical antipsychotic drugs. BL-1020’s beneficial effects on cognition were demonstrated in behavioral studies as well as in vivo microdialysis studies. Behavioral studies, conducted in collaboration with Prof. Jo Neil (School of Pharmacy, Bradford University, UK) have shown that BL-1020 reverses cognitive impairment induced by phencyclidine (PCP). Microdialysis studies, conducted in collaboration with Prof. Herbert Meltzer (Vanderbilt University School of Medicine, USA) have shown that BL-1020 enables dopamine efflux in the cortex and hippocampus (dopamine efflux in these areas has been associated with improved cognition). In extensive preclinical toxicology and safety pharmacology studies, BL-1020 has been shown to have a very high safety index.

BioLineRx completed a Phase Ia, single administration, double blind placebo control, safety trial in October 2007 conducted under the auspices of the Israeli Ministry of Health. A total of 48 healthy volunteers participated in the trial. Overall, the findings demonstrated the safety and tolerability of BL-1020. BL-1020 was not associated with any cardiac, neurological or psychological side effects.
 
BL-1020 was also tested in Phase Ib receptor occupancy (PET) trial completed in July 2007. In this trial, conducted under a U.S. FDA Investigational New Drug Application Process (IND) and the auspices of the Swedish Health Ministry, BL-1020‘s affinity to dopamine receptors was assessed in healthy volunteers. The trial demonstrated that BL-1020 binds to dopamine receptors at efficacious levels and that the drug need only be given once daily. The study also provided additional safety, tolerability and pharmacokinetic data.