• A potent and selective PAD4 inhibitor demonstrates efficacy comparable to an anti-TNFα biologic in a mouse model of arthritis
  
  

15 September 2026 – C4X Discovery Holdings Ltd ("C4XD"), a pioneering Drug Discovery company, today announces further progress in its small molecule PAD4 inhibitor programme. C4XD’s lead compound achieved activity comparable to an anti-TNFα biologic in a mouse collagen-induced arthritis (CIA) model. This result underlines the potential of the company’s oral small molecule programme, which could offer rheumatoid arthritis patients a more convenient alternative to injectable biologic therapy.

Nick Ray, CSO of C4X Discovery, commented: “The demonstration of efficacy in a relevant disease model is a key milestone in any drug discovery project. A lead compound from our small molecule PAD4 inhibitor programme has shown activity at 10mg/kg after oral dosing with activity equivalent to etanercept, an anti TNFα biologic that has been a cornerstone of rheumatoid arthritis treatment for close to three decades. To reach that level with an oral small molecule, coupled with its encouraging selectivity profile, we are confident that a pre-clinical candidate is within reach.”

Emma Blaney, CEO of C4X Discovery, said: “C4XD has a strong track record of partnering pre-clinical programmes at various stages in the drug discovery process; we plan to continue partnering discussions for our PAD4 programme during the remainder of 2026. Additionally, we continue to advance our α4β7 programme whilst holding partnering discussions, alongside recent clinical progress under our AstraZeneca-partnered NRF2 programme¹. We’d like to thank our staff and investors for their continued support to advance our programmes so that we can collaborate with the best partners to take them forward into the clinic.”

C4XD’s pipeline spans several high-value immuno-inflammatory indications. The company is currently advancing best-in-class oral α4β7 inhibitors alongside a first-in-class PAD4 programme, encompassing both innovative monotherapies and strategic combination approaches across multiple therapeutic areas.

Rheumatoid arthritis (RA) is a systemic autoimmune disease of the synovial tissue in the joints. Symptoms range from swelling and pain to bone erosion and debilitating joint destruction. Anti-Citrullinated Protein Autoantibodies (ACPAs) are found in up to 70% of RA patients, often years before clinical symptoms appear, suggestive of their role in driving disease². PAD4 is a key enzyme in the generation of the citrullinated antigens targeted by ACPAs, and in the formation of neutrophil extracellular traps (NETs), which contribute to a range of immune-mediated conditions including lupus, renal, cardiovascular and respiratory diseases. A small molecule PAD4 inhibitor offers pipeline-in-a-product potential across multiple high-value autoimmune and inflammatory indications with considerable unmet need. Alongside our α4β7 programme, PAD4 gives us another complementary mechanism across immuno-inflammatory disease.

1. https://c4xdiscovery.com/c4x-discovery-to-receive-milestone-payment-for-nrf2-exclusive-worldwide-license-agreement/
2. van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther. 2005;7(5):R949–58. doi: 10.1186/ar1767.

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About C4X Discovery

C4X Discovery (C4XD) is a pioneering Drug Discovery company, combining scientific expertise with cutting-edge technologies to efficiently deliver world leading next-generation oral medicines. Our enhanced molecular design capabilities deliver a highly differentiated approach to drug discovery, demonstrated by three high-value programmes successfully out-licensed to date. C4XD’s pipeline of small-molecule programmes spans several high-value immuno-inflammatory indications. The company is currently advancing a best-in-class oral α4β7 programme and a first-in-class PAD4 programme. Our strategy is to move these programmes to candidate stage where we look to out-license or collaborate with the best partners to execute clinical development and commercialisation.

For more information visit us at www.c4xdiscovery.com