MALT-1 Inhibitor Programme Update


C4X Discovery Holdings plc

(“C4XD”, “C4X Discovery” or the “Company”)

Profiling of C4XD lead series shows no UGT1A1 liability at clinically meaningful doses

 C4XD series potentially differentiated for safety profile

1 June 2023 – C4X Discovery Holdings plc (AIM: C4XD), a pioneering Drug Discovery company, provides an update on its MALT-1 inhibitor programme for cancer.  C4XD has successfully completed a preclincial study demonstrating its MALT-1 lead compounds are free of UGT1A11 liability shown by competitor chemistries.  The C4XD MALT-1 inhibitor programme is continuing to identify a shortlist of pre-clinical candidates for further development and a partnering programme has been initiated.

MALT-1 is one of the key regulators of B-cell receptor (BCR) and T-cell receptor (TCR) signalling.  Mutations that lead to 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.

Bilirubin is a toxic pigment produced naturally in the body as a result of the breakdown of red blood cells and is normally cleared in the bile by the enzyme UGT1A1.  Excessive bilirubin (hyperbilirubinemia) has been observed clinically in patients treated with a range of tyrosine kinase inhibitors, including BTK inhibitors, and has been associated with inhibition of UGT1A1 by these drugs.  BTK/MALT-1 combination therapies represent a desirable therapeutic dosing regimen and little or no activity against UGT1A1 by a MALT-1 inhibitor is essential to reduce UGT1A1 inhibition burden.

Dr Nick Ray, CSO of C4XD, said: 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.  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.”

  1. UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)

C4X Discovery Holdings plc

Mo Noonan, Communications+44 (0)7876 444 977

Panmure Gordon (UK) Limited (NOMAD and Broker) +44 (0)20 7886 2500

Freddy Crossley, Emma Earl (Corporate Finance)
Rupert Dearden (Corporate Broking)

Consilium Strategic Communications

Mary-Jane Elliott, Chris Gardner, Matthew Neal +44 (0)203 709 5700

C4X Discovery (“C4XD”) is a pioneering Drug Discovery company, combining scientific expertise with cutting-edge Drug Discovery technologies to efficiently deliver world‑leading medicines.  We have a highly valuable and differentiated approach to Drug Discovery through our enhanced candidate molecule design and patient stratification capabilities, generating small molecule drug candidates across multiple disease areas focused on immuno-inflammation.  Our commercially attractive portfolio ranges from early-stage target opportunities to late-stage Drug Discovery programmes and we have three commercially partnered programmes with one candidate in clinical development.

For more information visit us at www.c4xdiscovery.com or follow us on twitter @C4XDiscovery.