Citryll Raises €15M Series A for Antibody Development
pharmatechoutlook

Citryll Raises €15M Series A for Antibody Development

By Pharma Tech Outlook | Tuesday, July 23, 2019

The pharmaceutical sector is witnessing a gradual shift toward developing effective antibodies for autoimmune diseases, which will potentially lead to enhanced preventive care.

FREMONT, CA: Citryll, a Dutch biotech company, recently obtained a €15M Series A funding for the development of antibodies to fight autoimmune and inflammatory diseases. The antibody approach will potentially surpass the current treatment, which inhibits the innate immune system. The funding will be used for the clinical development of a lead antibody designed for the treatment of autoimmune condition lupus. It will also boost the preclinical development of antibodies aimed at treating rheumatoid arthritis and idiopathic pulmonary fibrosis.

The conventional treatment for autoimmune and inflammatory diseases suppresses inflammation, which in turn inhibits the ability to fight infections. However, Citryll plans on taking a unique approach, targeting the neutrophils, which are a type of white blood cells bolstering the innate human system. These cells form the first line of defense against the hostile pathogens.

When battling the invading pathogens, the neutrophils sacrifice themselves to lock up the attackers in cells composed of DNA and proteins. The cages are referred to as neutrophil extracellular traps (NETs). However, in the case of autoimmune and inflammatory diseases, the NETs can escalate the condition by releasing autoantigens and inflammatory molecules.

Citryll’s antibodies are designed to inhibit the production of NETs, thus preventing the weakening of the immune system and facilitating a focused treatment. NETs can enhance the effect of antibiotics in bacterial infections. Several researchers are also investigating targeting the neutrophil structures for the treatment of meningitis.

The primary therapeutic antibodies identified before optimization were designated as tACPA, and were found among cyclic citrullinated peptide (CCP) antibodies clone from B lymphocytes of RA patients. The tACPA’s cellular MoA showed signs of interfering in NET biology, using neutrophils from healthy donors as well as from RA and SLE patients. The therapeutic use of tACPA in an RA mouse test model led to inflammation, inhibiting the further inflammatory response and decreasing joint damage. The administration of prophylactic in two more RA mouse models also resulted in the prevention of inflammation.

The tACPAs can identify the citrullinated N-terminus of histone-2A and histone-4 present in human NETs. Neutrophils and aberrant NET formation mostly cause inflammation. NETs are critical for the development of autoimmunity in human RA, SLE, and several others. Also, when tested in IPF animal models, the tissue damage in the lung was inhibited by tACPA intervention. Hence, Citryll’s innovative approach has shown great promise in the development of antibodies for the treatment of autoimmune diseases. 

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