Mod-5014, a Novel Long-Acting FVIIa Proposing An Improved Prophylactic and On Demand Treatment For Hemophilic Patients Following SC and IV Administration – Comprehensive In -Vitro and In -Vivo evaluation In Preparation For Clinical Studies

摘要: Introduction Prolor Biotech Inc. is a clinical stage public company developing biobetter long acting versions of existing therapeutic proteins utilizing technology termed CTP. The involves fusion the C terminus peptide hCG to one or both ends target protein. was clinically validated and proven as safe efficient way for prolonging half-lives several while maintaining their biological activity. aim this extensive study characterize in vitro potency well –vitro interactions MOD-5014 (FVIIa-CTP ) with physiological inhibitors cofactors determine its pharmacokinetic (PK), pharmacodynamic (PD) term hemostatic effects relevant hemophilic animal models following IV SC administrations moving forward into studies . Methods FVII-CTP expressed CHO cells, purified activated CTP specific purification process. characterized SPR ex-vivo assays ( TEG TG). In order assess vivo effect , administered warfarin treated rats FVIII-/- mice, injection PK PD profiles were determined coagulation parameters (PT,aPTT ,TG FVIIa activity) at time dependent manner. addition, evaluated bleeding challenge by tail clip assay vein transection compared commercial rFVIIa. Results activity comparable FVIIa. PT thrombin generation administration superior those values maintained normal significantly longer post injection. half-life AUC 5 3.5 fold higher, respectively also Following administration, MOD-50149s bioavailability, shown be rFVIIa mice well. studies, had profound on survival rate, which more than 24 reduced duration intensity observed routes. Finally, toxicological rodents demonstrated that tolerable relatively high doses. Conclusion Attachments led markedly enhanced PK, increased exposure reflected AUC, improved recovery prolonged further supporting resulted bioavailability relative translated superior-vivo efficacy. attachment no significant impact in-vitro proposing similar mechanism action Our data suggest fused has potential frequency given demand potentially enable prophylactic treatment patients. Disclosures: No conflicts interest declare.