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Oct 23, 2012

Biotecnol, PolyTherics Ally on Anticancer Tribody Drug Conjugates

  • Biotecnol and PolyTherics formed a collaboration that aims to develop multispecific anticancer Tribody-drug conjugates (TDCs) that consist of Biotecnol’s Tribody molecules linked to cytotoxic payloads attached using PolyTherics’ site-specific ThioBridge™ linker technology. The companies will evaluate the resulting ThioBridge Tribody-drug conjugates in preclinical cancer models, and jointly look for licensing partners for the most promising candidates.

    PolyTherics’ ThioBridge platform has been developed to enable the conjugation of a range of therapeutic payloads to antibodies, antibody fragments, or scaffolds via specific sites and without impacting functional domains. “A key challenge facing developers of protein-drug conjugates is that the chemistry linking the targeting molecule to the toxic payload can lead to unstable, heterogeneous products,” remarks John Burt, PolyTherics’ CEO. “PolyTherics’ technology is site-specific, predictable, and results in stable and homogeneous conjugates. Combining these attributes with the versatility of Biotecnol’s Tribody platform has the potential to create the next-generation of targeted cancer therapies.”

    Biotecnol’s Tribodies are multifunctional recombinant antibodies, generated via the natural in vivo heterodimerization of Fab fragments to form a scaffold, onto which two additional binding moieties can be incorporated, including scFv antibody fragments, natural protein ligands, cytokines, receptor domains, tags, or protein toxins, small molecules, or radionucleotides. The firm claims the resulting molecules are stable and easy to produce in a single batch, without the need for any post-production processing other than purification. Tribodies are in addition produced in standard mammalian cell technology using well established methods.

    Biotecnol claims the technology has a number of advantages compared with other bispecific formats. In particular, trispecificity means one molecule can be dual-targeting with a T-cell effector function. And at about 100 KDa, the molecules are of a size that is between bispecific antibody fragments and IgG molecules, which the firm says represents an ideal balance between tumor penetration and half life. Its in-house pipeline includes Tribody candidates against triple-negative breast cancer, malignant melanoma, and gastric cancer.

    PolyTherics is leveraging a suite of technologies for the site-specific conjugation of therapeutic proteins. It’s three-platform PEGylation technologies are TheraPEG™ for PEGylation across a native disulfide bond, CyPEG™ for PEGylation at a thiol on free cysteine, and HiPEG, for PEGylation at a histidine residue. The firm has also developed a low-viscosity polymer and glycopolymer for targeted delivery of therapeutic proteins.

    Last month Pro Bono Bio exercised its option to take an exclusive global licence to PolyTherics’ TheraPEG technology for the development and commercialization of a TheraPEG-FVIII product. The option exercise follows a feasibility program to develop and evaluate a long-acting PEGylated form of Factor VIII for the treatment of hemophilia A. 


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