Therapeutic Areas

Rheumatoid Arthritis

As a next step in CIT-013’s clinical development, Citryll will carry out a Phase 2a PoC in a well-studied autoimmune disease, 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.

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 NET pathway plays a pivotal role in Rheumatoid Arthritis

Recently, the elevation of NETosis and NETs has been well established in RA disease pathology. NETs and activated enzymes released by NETosis significantly contribute to the pol of citrullinated auto-antigens characteristic of the disease. NETosis and its related markers have been shown to be upregulated in RA patients and correlate with disease activity.

Citryll’s unique approach with CIT-013 reduces NET levels in inflamed tissue and thereby affects multiple pathogenic factors: cytotoxic histones, DNA, granule contents, DAMPs and auto-antigens. Furthermore, reduction of NET levels resets the activation status of lymphocytes and aberrant differentiation of cell types such as bone degenerative osteoclasts.

In pre-clinical mouse models of arthritis, Citryll’s lead compound CIT-013 has demonstrated therapeutic and dose-dependent anti-inflammatory effect, with bone and cartilage protective consequences, thus confirming the causal relation of NETs and phenotypic progression in these models.

Citryll’s own published data on pre-clinical mouse model of arthritis further supports the claim of therapeutic efficacy of the antibody. In addition to preclinical efficacy data, our data also 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, a proof-of-concept study in RA is expected to start later this year.

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