DELIVERY TECHNOLOGIES


New technologies enabling better biopharmaceuticals


PolyTherics has a range of proprietary precision chemistry and novel polymer technologies that are applicable in the development of biopharmaceutical products based on optimised pharmacokinetics and pharmacodynamics, superior protein-drug conjugation and glycopolymer-mediated targeting of protein-carbohydrate interactions.


UK-based PolyTherics Ltd has developed a comprehensive portfolio of proprietary chemical technologies for the modification of peptide and protein drugs to improve their delivery characteristics, slow their elimination from the human body, enhance their physicochemical properties and optimise their in-vivo efficacy and safety profiles. Modified peptide and protein drugs have the potential to increase clinical benefit, reduce treatment costs and improve patient compliance. PolyTherics’ technologies include the site-specific conjugation of proteins, peptides, antibodies and other therapeutic entities; low-viscosity polymers; and targeted drug delivery. The company’s business model offers product-specific technology licences and collaborative programmes. Many of these programmes are progressing towards IND and the initiation of clinical development in collaboration with development partners. PolyTherics is VC-funded and has raised £7.75 million in total. The company acquired Warwick Effect Polymers in January of this year and now has 33 employees, including 16 PhDs, based in dedicated UK lab and office facilities in central London and Coventry.


“Product stability and half-life are the main properties that require improvement in the translation of a therapeutic peptide or protein candidate into a viable product,” says Dr John Burt, PolyTherics’ CEO. “Strategies to improve pharmacokinetics include the optimisation of formulations, development of slow-release systems such as microspheres, and chemical modifications to improve the stability of the peptide, such as amino acid substitution, increasing the size of the peptide drug to extend the in-vivo half-life, and attachment to other proteins, polymers or other chemical entities.”


One such polymer modification is via PEGylation – the covalent conjugation of poly(ethylene glycol) to molecules – this improves a product’s circulating half-life in vivo, its solubility and its stability, enhances resistance to proteolysis, and reduces immunogenicity. There are currently eleven PEGylated therapeutic products on the market, including the recently approved EPO mimetic peptide, hematide, developed by Affymax and Takeda.


“In considering a PEGylation strategy, or indeed any conjugation modification to a protein, the efficiency of the process as well as the stability and heterogeneity of the product are key criteria to be addressed in any technology


selection process. PolyTherics’ conjugation chemistries achieve site- specific


conjugation at higher yields than alternative


Functionalised PEG reagent production in PolyTherics' laboratories. 34 sp2 Inter-Active July/August 2012


approaches, with a


simpler purification process to obtain the desired product,” Burt says.


TheraPEG PEGylation technology PolyTherics’ technologies enable the development of better biopharmaceuticals through PK/PD optimisation, the development of protein drug conjugates, new-format products and targeted delivery. The company’s patented technologies are TheraPEG™, enabling conjugation across a native disulfide bond; HiPEG™, for conjugation at polyhistidine; CyPEG™ for conjugation at a thiol group on free cysteine; PolyPEG™ for production of low-viscosity PEG-based comb polymers; and GlycoPol™ glycopolymers to target sugar receptors. These technologies can be applied to develop novel proteins, peptides, ‘biobetters’, antibodies, antibody fragments and domain antibodies, siRNA, aptamers and scaffolds for improved drug delivery and therapeutic performance.


The optimisation of PK/PD employs the company’s novel conjugation technologies such as TheraPEG. By selectively targeting accessible disulfide bonds, without the need for protein re-engineering, the process retains the tertiary structure of the protein and provides more stable cross-linking. “Interferon β-1b is an ideal target for TheraPEG, says Burt. “There are 2.5 million multiple sclerosis patients worldwide and the market for IFN β products is valued at $6 billion. Currently there is no marketed PEGylated IFN β. PolyTherics has been able to target the protein’s single accessible disulfide bond and has established an efficient process with a low molar PEG:protein ratio. The extended half-life of TheraPEG™ IFN β-1b has been demonstrated in vivo, and the conjugate is now the subject of a licence agreement between PolyTherics and Nuron Biotech.” Other examples of the application of TheraPEG include the PEGylation of Factor IX


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