C4X Discovery Holdings PLC (AIM:C4XD) has successfully completed a crucial preclinical study showing its MALT-1 inhibitors for cancer are free from a common problem seen in competitor drugs, known as UGT1A1 liability.
This breakthrough relates to MALT-1, a key factor in regulating signals in our bodies' B-cells and T-cells.
Malfunctions of MALT-1 have been tied to aggressive types of non-Hodgkin B-cell lymphoma, a type of cancer.
Inhibiting the protein could be a game-changing therapy for MALT-1-driven cancers and may have even wider applications in other blood disorders, solid tumours and inflammation.
The term UGT1A1 liability might sound complex, but it essentially relates to a toxic pigment called bilirubin, which our bodies naturally produce when breaking down red blood cells.
It is usually cleared away by an enzyme, UGT1A1. However, some drugs can inhibit this enzyme, leading to excessive bilirubin in the body, a condition known as hyperbilirubinemia. C4XD's MALT-1 inhibitors do not inhibit UGT1A1, eliminating this potential side effect.
The inhibitors were identified using the company's Conformetrix technology, which Dr Nick Ray, C4XD's chief scientific officer, said has yet again delivered "best-in-class" molecules.
They have the potential to be used on their own (as a monotherapy), or in combination with Bruton tyrosine kinase inhibitor drugs.
"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," Ray added.
"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."