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• W2565140874 abstract "Abstract Abstract 1114 Background: Prolor Biotech Inc. is a clinical stage public company developing biobetter long acting versions of existing therapeutic proteins utilizing a technology termed CTP. The technology involves fusion of the C terminus peptide of hCG to one or both ends of the target protein. The technology was clinically validated and proven as a safe and efficient way for prolonging the half-lives of several therapeutic proteins while maintaining their biological activity. Aims: To determine the pharmacokinetic (PK), pharmacodynamic (PD) and long term hemostatic effects of FVIIa-CTP in murine FVIII−/− mice following IV and SC administrations and to characterize FVIIa-CTP in vitro mechanism of action. Methods: FVIIa-CTP was expressed in CHO cells, purified and activated utilizing a purification process involving a CTP specific step. FVIIa-CTP was administered to FVIII−/− mice, and following IV and SC injection the PK and PD profiles were determined. In addition, the long term hemostatic effect was evaluated following bleeding challenge (tail clip assay and in a Tail Vein Transection) as compared to commercial rFVIIa. FVIIa-CTP in-vitro characteristics were also evaluated. Results: FVIIa-CTP PK parameters following IV administration, as assessed by a clotting assay, were superior to those of rFVIIa. Its half-life and AUC were 5 and 3.5 fold higher, respectively. A 2 fold improvement in the recovery was observed 15–30 minutes post dosing. Thrombin generation parameters were also superior in these studies. In a Tail Vein Transection study, FVIIa-CTP had a profound effect on survival, which was maintained for more than 24 hours. Reduced duration and intensity of bleeding was also observed in the tail clip study. Following SC administration, FVIIa-CTP's bioavailability, Cmax and half life were superior to commercial rFVIIa in both rats and hemophilic mice models. Correction of thromboelastograply in FVIII −/− mice plasma was maintained longer with FVIIa-CTP than with rFVIIa. Conclusion: Attachments of CTP to FVIIa led to a markedly enhanced PK, increased exposure, as reflected by AUC,improved recovery and a prolonged hemostatic effect in hemophilic mice with a comparable specific activity to rFVIIa. In addition, SC administration of FVIIa-CTP resulted in improved bioavailability and exposure was significantly prolonged relative to IV administration. Our data suggest that CTP fused FVIIa has the potential to significantly improve the prophylactic and on demand treatment of hemophilic patients. Disclosures: Seligsohn: prolor biotech: Consultancy, clinical advisor Other." @default.
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• W2565140874 date "2012-11-16" @default.
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• W2565140874 title "Factor VIIa-CTP, a Novel Long-Acting Coagulation Factor, Displays a Prolonged Hemostatic Effect and Augmented Pharmacokinetics and pharmacodynamics Following IV and SC Administration in Hemophilic Animal Models" @default.
• W2565140874 doi "https://doi.org/10.1182/blood.v120.21.1114.1114" @default.
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