MALT-1 Inhibitor Programme Update

C4X Discovery Holdings plc

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

Positive key preclinical study positions programme for partnering

19 January 2023 – C4X Discovery Holdings plc (AIM: C4XD), a pioneering Drug Discovery company, provides an update on its MALT-1 inhibitor 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.

Dr Nick Ray, CSO of C4XD, said: “Using our NMR-based ‘shapes in solution’ technology, Conformetrix, led to the generation of a number of structurally-distinct series, now in Lead Optimisation. Showing activity comparable to the industry’s lead clinical compound with our first compound in this key xenograft model, coupled with the range of improved compounds following behind, gives us confidence in nominating candidate-quality molecules within the next six months.

“At C4XD we have a reputation for producing high quality small molecule candidates as seen in our recent out-licensing agreement with AstraZenca worth up to $401 million. MALT-1 is a highly desirable target for an oral therapeutic and this study is a key trigger to initiate early-stage conversations with potential partners in the pharmaceutical industry in order to maximise the value of this programme.

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, which are developed by our partners for the benefit of patients. We have a highly valuable and differentiated approach to Drug Discovery through our enhanced DNA-based target identification and candidate molecule design capabilities, generating small molecule drug candidates across multiple disease areas including inflammation, oncology, neurodegeneration and addictive disorders. Our commercially attractive portfolio ranges from early-stage novel target opportunities to late-stage Drug Discovery programmes ready for out-licensing to partners and we have three commercially partnered programmes with one candidate in clinical development.

We collaborate with leading pharmaceutical and life sciences companies to enrich our expertise and take our assets through pre-clinical and clinical development. Through early-stage revenue-generating licensing deals, we realise returns from our high value pre-clinical assets which are reinvested to maximise the value of our Drug Discovery portfolio.  For further information see