Roche is discontinuing its partnership with the Wilex subsidiary Heidelberg Pharma for the development of antibody-targeted amanitin conjugates or ATACs. The licence agreement was signed in 2013 and expanded in October 2014.

Roche has recently increased the focus of its oncology research strategy on cancer immunotherapies and deprioritised other internal and external oncology research programmes accordingly. Affected by this deprioritisation are the collaborative research efforts with Heidelberg Pharma, which, according to a number of industry insiders have, in recent years, progressed well, are on schedule.

Financial outlook for 2015
As a consequence of the termination of existing collaborative efforts to develop and identify novel antibody-targeted amanitin conjugates (ATACs), Wilex revised today its financial outlook for the current financial year. Due to lower sales revenues Wilex’s cash reach is reduced from the end of the second quarter 2016 to the first quarter of 2016.

New ADC Technology
Wiley subsidiary Heidelberg Pharma has developed a new ADC technology based on the most potent RNA-polymerase II inhibitor amanitin, a bicyclic octapeptide isolated from the Green Deathcap mushroom Amanita phalloides. Amanitin interferes with the eukaryotic transcription process at very low intracellular concentrations.  As a result, it is an ideal drug for the use with antibodies binding at low-copy number antigens.

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As part of their ongoing development program, researchers at Heidelberg Pharma have shown outstanding activity of amanitin-based ADCs in therapy-resistant tumor cells at picomolar concentrations.  To-date, researchers have been able to determine  tolerability and therapeutic window of amanitin-ADCs in different rodent and non-human primate models. Because amanitin has a water-soluble structure, resulting in ADCs with low tendency for aggregation, using a higher drug to antibody ratios or DAR.

Researchers at Heidelberg Pharma have also identified sites in amanitin that are suitable for linker integration without diminishing its binding to the target enzyme RNA polymerase II. These linker structures have been successfully modified with reducible disulfide groups and protease-cleavage sites and thus optimized for the individual antibody structure.

Last Editorial Review: August 12, 2015

Feature Image: Amanita phalloides Circa. 1890s Joseph Bridgham (1845-1915) unpuplished watercolor and pen & ink drawing Farlow Archives of Cryptogamic Botany. Feature image Courtesy: Farlow Archives of Cryptogamic Botany. This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license. CC BY-SA 3.0

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