Rheumatoid Arthritis
Rheumatoid arthritis disrupts millions of lives worldwide
Citryll is currently in Phase 2a trials for CIT-013 in rheumatoid arthritis (RA).
RA is a prevalent, chronic autoimmune disease characterized by inflammation of the joints. Its hallmark symptoms include joint pain, stiffness and swelling, often leading to reduced mobility and severely impacting patients’ quality of life. Despite advances in treatment, only about 30% of patients achieve durable remission through current therapies.
RA is characterized by the presence of autoantibodies to self-antigens, particularly, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). These can be present many years before the onset of disease and are linked to RA pathogenesis.
CIT-013 suppresses inflammation and progressive bone and cartilage erosion in mouse model of arthritis
Red: Cartilage; Blue: Bone; Pink: Inflammatory cell influx. Adapted from Citryll publication: Chirivi et al 2021. DOI: 10.1038/s41423-020-0381-3
The ET pathway plays a pivotal role in rheumatoid arthritis
There are significant challenges with current approaches in RA, with a high proportion of patients not achieving adequate disease control. Citryll targets a key driver of inflammation in RA, going beyond individual pathway management and symptom treatment.
The elevation and persistent formation of ETs has been well established in RA disease pathology. ETs and activated enzymes released by ETosis significantly contribute to the progression of the disease, with ETosis and its related markers shown to be upregulated in RA patients and show a strong correlation with disease activity.
Citryll’s unique approach inhibits the formation of ETs and enhances the clearance of ETs while preserving normal intracellular functions. In pre-clinical mouse models of arthritis, Citryll’s lead asset, CIT-013, has demonstrated therapeutic and dose-dependent anti-inflammatory effect, with bone and cartilage protective consequences, thus confirming the causal relation of ETs and phenotypic progression in these models.
In addition to preclinical efficacy data, Citryll’s data confirms the presence of CIT-013’s target in synovium tissue from RA patients providing further rationale to prioritize RA as key indication.
Following the successful completion of safety studies with our lead antibody CIT-013, the Phase 2a study in RA started in July 2025.
Elevated CIT-013 epitope in RA synovial tissue with moderate to marked active synovitis
Three representative images of H&E-stained synovial biopsies (left) and CIT-013’s epitope (magenta staining in boxes on the right). Biopsies taken from RA patients with minimal active synovitis (a), moderate active synovitis (b) and moderate to marked active synovitis (c). The scale bar for H&E staining is 2mm, and for CIT-013 staining is 200µm.
Adapted from Citryll’s publication:
Van der Linden et al (2023) DOI:10.1080/19420862.2023.2281763
Clinical trial opportunities for patients
Citryll is conducting clinical trials for CIT-013, an investigational therapy developed to address Rheumatoid Arthritis (RA) and Hidradenitis Suppurativa (HS). This clinical research seeks to understand CIT-013’s potential effectiveness, safety, and impact on patient quality of life. We expect two clinical trials to start by mid 2025.