C4X Discovery Holdings PLC MALT-1 Inhibitor Programme Update (2493B)
June 01 2023 - 2:00AM
UK Regulatory
TIDMC4XD
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 or follow
us on twitter @C4XDiscovery.
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