Colorectal cancer: Results of Heidelberg Pharma's research cooperation with MD Anderson Cancer Center published

WILEX AG has announced that pioneering study results on the Antibody Targeted Amanitin Conjugates (ATACs) technology have been published in the peer-reviewed journal Nature, in a report by the Department of Cancer Biology, University of Texas MD Anderson Cancer Center and scientists of Heidelberg Pharma, a subsidiary of WILEX.

In preclinical studies, research groups from MD Anderson and Heidelberg Pharma demonstrated the extraordinary efficacy of ATAC therapeutics in the treatment of a colorectal cancer subpopulation with alterations in the status of the tumor suppressor gene TP53. The reason for these alterations is the co-deletion of one copy of TP53 and the neighbouring POLR2A gene, which codes for the ATAC-target RNA polymerase II. Such hemizygous gene status of TP53 and POLR2A leads to reduced expression of RNA polymerase II and thus the significantly higher sensitivity of cancer cells towards ATACs. In preclinical, in vitro and in vivo, studies ATACs exhibited an approximately ten times higher antitumoral activity on POLR2A hemizygous cancers compared to homozygous cancers. Initial data indicates similar gene status alterations in other tumors, making ATACs a promising therapeutic strategy for patients suffering from highly resistant malignancies. In a clinical setting the s! election of patients based on TP53 or POLR2A gene status will allow the expansion of the therapeutic window of ATACs and ensure high efficacy while minimizing toxicity.

Professor Andreas Pahl, CSO of Heidelberg Pharma GmbH, commented: "The use of TP53 and POLR2A gene status as a biomarker for ATAC sensitivity could allow the stratification of patients most likely to benefit from treatment with ATACs. Patient selection with respect to payload sensitivity is a new approach in the field of antibody-drug conjugates (ADCs) and could help to circumvent the current limitations of this class of therapeutics."

Professor Xiongbin Lu, MD Anderson Cancer Center, said: "Today CRC patients with altered TP53 gene status have a non-favourable prognosis and only a few beneficial treatment options. With the discovery of POLR2A as a therapeutic target for p53 mutant tumors, ATACs could significantly improve the therapeutic outcome in such cancer populations."