PolyTherics is teaming up with researchers at University College London (UCL) in the U.K. to develop a new protein-based therapy for treating antiphospholipid syndrome (APS). The partnership aims to combine PolyTherics’ site-specific PEGylation technology with proteins developed by professor Anisur Rahman’s team at UCL, which block the binding of antiphospholipid antibodies to phospholipid-protein complexes in the bloodstream.
“The challenge for many potential protein-based treatments is getting them to remain in the body long enough to have a therapeutic effect,” remarks Keith Powell, PolyTherics’ CEO. “We are excited to be working with professor Rahman to achieve this for a much-needed treatment for this serious but still under-diagnosed condition.”
APS is an autoimmune disease that can cause blood clots, stroke, or recurrent miscarriages, PolyTherics explains. Patients with the condition generate antibodies that bind to their own phospholipid-protein complexes in the blood and are believed to trigger changes that affect blood clotting. The only treatment for the disease, which mainly affects young people, is to give anticoagulants.
PolyTherics has developed a range of PEGylation technologies designed to attach PEG to a specific site on the protein or peptide of interest. The firm claims this ability results in more homogeneous PEGylated products than those produced by traditional PEGylation methods through which the PEG molecule can attach to multiple sites, creating a mixture of proteins with the PEG at different positions.
Three PEGylation technologies are being exploited both in house and through licensing and collaboration agreements. TheraPEG™ is designed to affect PEGylation across one or more disulfide bonds naturally present in the target protein. HiPEG™ adds the PEG molecule at a histidine tag expressed at either one or both ends of a protein. CyPEG™ involves PEGylation at the thiol group of free cysteine molecules within a protein or peptide.
PolyTherics’ lead in-house projects are focused on a HiPEG IFN α-2a and a TheraPEG IFN β-1b. Both programs are expected to be outlicensed for clinical development and commercialization. The firm claims in vitro studies have shown the HiPEG IFN α-2a candidate demonstrates eight-fold higher activity than a marketed PEGylated interferon, and a comparable half-life in preclinical studies.
Earlier this month PolyTherics announced a deal with microbial fermentation CMO, DSM BioSolutions, for the process development and manufacture of HiPEG IFN α-2a for both preclinical and clinical development.