Dutch biotech Citryll raises $17 million in first-round financing as investors are attracted by a new approach to tackling autoimmune diseases such as lupus and rheumatoid arthritis.
Citryll, a spin-off of a contract research and laboratory tool venture known as ModiQuest in 2015, is developing a platform based on antibodies that prevent the formation of neutrophil extracellular traps (NETs), reports PMLive.
What are NETs?
NETs are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind to invading pathogens and are a part of the body’s immune defense that doesn’t involve damage to host cells.
Enter a Dangerous World
The neutrophil is a powerful and vigilant defender constantly prowling the bloodstream in search of pathogenic invaders. When they encounter a target, it is swiftly engulfed and digested by the voracious scavenger. After the kill, the hunter does something unexpected: it casts a net to capture additional prey.
Neutrophil’s are efficient assassins who expect to die, not reproduce. Their DNA is utilized as yet another weapon in their arsenal. When a pathogen is encountered, the neutrophil activates an enzyme called PAD4 to unpackage a tightly coiled chromosomal DNA into loose strands of sticky web-like material. The nuclear contents are ejected from the neutrophil forming a deadly net composed of DNA strands interconnected by histones, and impregnated by lethal antimicrobial agents including myeloperoxidase, neutrophil elastase and defensins. The newly formed net is set, capturing and killing any invading bacteria lucky enough to swim into its embrace.
Mission Accomplished- Not so Fast
Once its mission is complete, its toxic net must be deactivated and destroyed. They end up chopping the DNA into smaller fragments that are easily ingested. Macrophages move into the area and dispose of the remaining net fragments to eliminate all traces of the pathogenic infection. Unfortunately, this defense sword wields two edges.
Failure to completely remove net fragments can result in the formation of auto-antibodies directed against net components, including DNA, histones and PAD4. These auto-antibodies can ultimately result in the development of autoimmune diseases, including lupus and rheumatoid arthritis.
The Focus: Autoimmune Disorders
In some autoimmune disease research, it is thought that NETs inadvertently react to host cells, stimulating the release of autoantigens—particularly citrullinated proteins—as well as inflammatory proteins and other toxic compounds, reports PMLive.
Developing a Way to Interfere with NETs Production
Citryll’s funding will support its proprietary program called tACPA, which is designed to interfere with the production of NETs (the deadly killers described above), a process catalyzed by the peptidyl arginine deiminase (PAD) enzyme pathway. tACPA binds citrullinated histones that are believed to be essential for NET formation.
Citryll Potential Differentiation
Bristol-Myers Squibb (via $600 million acquisition of Padlock Therapeutics in 2016) and other ventures are working on small molecule PAD inhibitors of autoimmune disease reports PMLive. However, Netherlands based Citryll believes its approach will be superior. It works downstream of PAD. Hence its impact is more specific to the disease-associated Nets and won’t involve blockade of normal PAD functions that can lead to adverse side effects.
CEO Helmuth van Es is banking on the Citryll assumption that drugs that interfere with NETs and their production “have the potential to create game changing new treatments to prevent or treat human diseases.” Mr. van Es notes “Citryll’s approach does not broadly target inflammation or acquired immunity, instead it extinguishes the source of autoantigens and (NET)-derived toxic molecules in the safest way possible.”
The funds are coming from ModiQuest, BOM Brabant Ventures, BrightGene and Curie Capital.