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While sub-threshold concentrations of each ligand alone did not alter basal spinogenesis, combined sub-threshold concentrations of 30 " M Dihexa and 2.5 ng/ml HGF or 10 " 13 M Nlel -AnglV and 2.5 ng/ml of HGF produced a near ceiling effect, similar to biological responsive doses of each ligand alone (Figure 1 1 A and B)

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31 Previous clinical trials (including two Phase 1 and one Phase 2a study) could demonstrate that continuous subcutaneous ND0612 delivery yielded steady-state plasma concentrations estimated to be in a therapeutic window