Production and Characterization of Mod-4023, a LONG Acting Growth Hormone Supporting Clinical and Commercial Drug Product Supply

Background: 

Prolor Biotech Inc. is a clinical stage public company developing long acting therapeutic proteins utilizing a technology called CTP. The technology involves fusion of the C terminus peptide of hCG, which is a highly O-glycosylated peptide, to the target protein. CTP enabled the production of a long-acting hGH (MOD-4023), which supports a single weekly injection in growth hormone deficient patients. MOD-4023 is manufactured as a non-viscous liquid formulation.

Aims:

Characterization of MOD-4023 drug substance and drug product with respect to the protein quality attributes process reproducibility

Methods:

MOD-4023 characterization was carried out by applying various acceptable analytical methods including glycosylation profiling and serine site occupancy, Capillary Zone Electrophoresis (CZE) and peptide mapping.  The pharmacological characteristics of MOD-4023 have been analyzed in vitro utilizing stable GH receptor expressing cells while the binding affinity of MOD-4023 to the Growth Hormone Receptor (GHR) was assessed by BIAcore analysis.

Results:

Glycoprofyling analysis of different batches shows that the major O-glycan structure in MOD-4023 is mono-sialylated core 1 with comparable site occupancy of the O-glycans in MOD-4023 between different batches. The high glycosylation levels contributes to the significant increased hydrodynamic volume of MOD-4023 as compared to recombinant hGH, which results in the elongated circulating time of MOD-4023. Similar peptide map profiles of MOD-4023 batches are obtained supporting the consistency of the drug substance primary structure in each batch. Comparable results for different batches were also obtained using on CZE analysis. MOD-4023 potency was assessed in vitro, utilizing cells stably expressing the human growth hormone receptor. MOD-4023 was shown to bind and activate the human GHR. MOD-4023 drug product has a low viscosity and consequently can be easily delivered using 31G needle.

Conclusion:

MOD-4023 manufacturing process is robust, producing a highly reproducible O-glycosylated product .Based on these findings and combined with its excellent safety profile and significant prolonged GH activity MOD-4023 has the potential to replace the daily injections of hGH now required for the treatment of GH deficiency with a weekly regimen.