C4X Discovery Holdings plc provides an update on its MALT-1inhibitor programme. Over-expression or over-activation of MALT-1 has been observed in a range of lymphomas and leukemias such as MALT lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia, suggesting that targeting of MALT-1 is a viable therapeutic strategy for treating haematological cancers. Building on promising in vitro, in vivo and pharmacokinetic data, C4XD has now successfully demonstrated anti-cancer activity for one of its lead molecules in a preclinical xenograft study.

Following oral dosing at 30mg/kg, significant tumour growth inhibition was observed. This result is comparable to data obtained from Johnson & Johnson's clinical compound JNJ-67856633 which is now in a Phase I clinical trial. The C4XD MALT-1 inhibitor programme has now advanced into the preclinical candidate selection phase.

MALT-1 is one of the key regulators of B-cell receptor (BCR) and T-cell receptor (TCR) signalling. Mutations that lead to constitutive activation of MALT-1 are associated with aggressive forms of non-Hodgkin B-cell lymphoma and inhibition of MALT-1 has potential therapeutic applicability as a mono therapy for MALT-1-driven cancers and in combination with BTK inhibitors across multiple haematological indications, as well as broader potential in solid tumours and inflammation.