REG - C4X Discovery - MALT-1 Inhibitor Programme Update

C4X Discovery HoldingsAnnouncement

01/06/2023 07:00

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RNS Number : 2493B  C4X Discovery Holdings PLC  01 June 2023

C4X Discovery Holdings plc

 

("C4XD", "C4X Discovery" or the "Company")

 

MALT-1 Inhibitor Programme Update

 

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 UGT1A1(1) 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)

 

- Ends -

 

Contacts

 

 C4X Discovery Holdings
 Mo Noonan, Communications                                 +44 (0)787 6444977

 Panmure Gordon (UK) Limited (NOMAD and Broker)
 Freddy Crossley, Emma Earl (Corporate Finance)            +44 (0)20 7886 2500
 Rupert Dearden (Corporate Broking)

 C4X Discovery Media - Consilium Strategic Communications
 Mary-Jane Elliott, Chris Gardner, Matthew Neal            +44 (0)203 709 5700

 

Notes to Editors:

 

About C4X Discovery

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
(http://www.c4xdiscovery.com) or follow us on twitter @C4XDiscovery.

 

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