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Jul 6, 2012

Cytotoxic Warheads at Forefront of Anticancer Collaboration

  • Cancer Research Technology (CRT) and newly established Swiss firm ADC Therapeutics (ADCT) inked a collaboration to develop antibody-drug conjugates (ADCs) based on CRT’s antibodies and peptides, and ADCT’s anticancer cytotoxic ‘warheads’ and linker chemistries. CRT is the commercial arm of Cancer Research U.K., and holds the IP rights to a range of the latter’s tumor-targeting antibodies. Under terms of the deal ADCT will initially fund preclinical studies with ADCs developed through the collaboration in a range of cancer models.

    ADCT was established in March by Celtic Therapeutics Management to progress an initial pipeline of 10 ADC programs targeting multiple major cancers. The firm has a partnership with Spirogen (which is also majority owned by Celtic Therapeutics Management) to develop ADC products. Spirogen and CRT both also hold stakes in ADCT, which starts out with an initial pot of $50 million in funding from Celtic Therapeutics Management.

    Spirogen’s killing agents are based on a pyrrolobenodiazepine (PBD) technology developed in partnership with University College London. In addition to the ADC collaboration with ADCT, the firm is developing a pipeline that comprises two DNA minor-groove binding, interstrand cross-linking PBD dimer molecules, SG2000 and SG2285. SG2000 is a C2-unsaturated PBD dimer currently undergoing Phase II ovarian clinical trials in the U.S., with further trials planned in Europe. The preclinical candidate SG2285 is a PBD dimer C11-prodrug that is activated by hydrolysis. Spirogen claims the active component, SG2202, is even more potent than SG2000.

    Preclinical development is also ongoing with the DNA minor groove-binding indolecarboxamide drug centanamycin (AS-I-145/NSC 716970), which was originally designed by researchers at Hope University as a less toxic, achiral analog of CC-1065 and duocarmycin. The firm says initial efficacy studies have been undertaken in animal xenograft models of glioma, lung, breast, and ovarian cancers. Further preclinical studies are also in progress at the National Cancer Institutes.

     


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