Science of ETosis
Pioneering approach targeting ET-driven inflammation
White blood cells, as neutrophils and eosinophils, are our body’s first line of defense against pathogens. One of their defense mechanisms is the release of Extracellular Traps (ETs): web-like structures composed of DNA, histones, and antimicrobial proteins. While ETs play a crucial role in the innate immune response, excessive ET formation can contribute to tissue damage and chronic inflammation.
The association of elevated ETs with active inflammatory disease has been described in a growing list of acute and chronic inflammatory conditions. Citryll is pioneering the development of novel therapeutics that target ET-driven inflammation by specifically targeting citrullinated histones, a hallmark of ETs, with its therapeutic monoclonal antibody, CIT-013.
The process of ETosis
The importance of close control of ETosis became clear in recent years as researchers identified that aberrant release and impaired degradation leads to the sustained presence of pro-inflammatory ETs in tissue which is associated with a variety of inflammatory diseases.
ETosis is a highly organized process that can be separated into distinct stages: 1) chromatin reorganization within the nucleus, 2) breaching of the nuclear membrane followed by chromatin decondensation within the cytoplasm, and 3) plasma membrane rupture leading to chromatin release and diffusion into the extracellular space.
| Healthy Neutrophil | Stage 1 | Stage 2 | Stage 3 | ||
|---|---|---|---|---|---|
Merge |
 |
 |
 |
 |
 |
- Plasma membrane
- DNA
ETs in acute and chronic inflammatory diseases
The association of elevated ETs and active inflammatory disease has been described in a growing list of acute and chronic inflammatory diseases, including rheumatoid arthritis (RA), hidradenitis suppurativa (HS), and several others. The detrimental role of ETs in disease is a consequence of several elements with ETs being pro-inflammatory, cytotoxic to surrounding tissue, a source of autoantigens, and diverting the differentiation of cells often with pathogenic phenotypes. As a consequence, the reduction of ET levels in inflamed tissue has become a therapeutic approach of increasing interest for the treatment of inflammatory diseases.
Citryll is a leader in developing novel therapeutics that target ET driven inflammation with its therapeutic monoclonal antibody, CIT-013, by specifically targeting citrullinated histones, a characteristic feature of ETs. The anti-inflammatory effect of CIT-013 has been successfully demonstrated in numerous preclinical models and safety and tolerability have been demonstrated in RA patients and healthy volunteers.
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.