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C4X Discovery Holdings PLC on Thursday said it has completed its preclinical study showing that its MALT-1 lead compounds are free of UGT1A1 enzyme liability at clinically meaningful doses, unlike competitor chemistries. The Manchester, England-based drug discovery company said it is identifying a shortlist of preclinical candidates for further development, and has commenced a partnering programme. MALT-1 is a regulator of B-cell and T-cell signalling, mutations which lead to the activation of MALT-1 which is associated with aggressive forms of non-Hodgkin B-cell lymphoma. The firm said excessive bilirubin - a toxic pigment usually cleared in the bile by the UGT1A1 enzyme - has been observed in patients treated with tyrosine kinase inhibitors used by competitors. ‘Yet again, our Conformetrix technology has delivered molecules that have the potential to be best-in-class. Building on promising anti-cancer activity in a preclinical xenograft study, we have now favourably observed little or no inhibition of UGT1A1 at clinically meaningful concentrations, whereas representative examples from other clinical and pre-clinical programmes showed significant UGT1A1 activities,’ said Nick Ray, chief scientific officer. ‘We believe this is due to the degree of chemical differentiation in the C4XD series compared to competitors and we are confident of identifying a pre-clinical candidate shortlist with a desirable safety profile in the near future.’ C4X shares closed down 3.3% to 15.55 pence each in London on Thursday. Copyright 2023 Alliance News Ltd. All Rights Reserved.
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