Citryll develops a first in class therapeutic antibody that targets Neutrophil Extracellular Traps (NET) formation for the treatment of a range of human diseases with potential for SLE, RA, vasculitis, IPF and other indications.
The initial therapeutic antibodies designated therapeutic Anti- Citrullinated Protein Antibodies or tACPAs, and prior to optimisation to CIT-013, were identified among ACPAs cloned from RA patient B lymphocytes. We have since demonstrated tACPA’s cellular MoA to be interfering with NET biology, using primary human neutrophils from healthy donors as well as RA and SLE patients and numerous in vivo pharmacology studies.
Near human lead antibodies were generated with appropriate potencies and favourable characteristics for development including low aggregation, good stability and good production in CHO based stable cell lines. The development candidate CIT-013 was selected from a this set of optimised antibodies. The production of CIT-013 drug substance and drug product is being conducted by Lonza including cell line generation, cloning, bioreactor scaling, process and formulation development, technical batch and GMP lot production.
In summary, the current status is: preclinical proof of concept using SLE and RA patient neutrophils, 2 animal models for RA, early data in IPF and colitis, sepsis model and pristane induced NET formation. We are currently expanding preclinical data set by testing in additional therapeutic models.
NETosis inhibition is expected to decrease auto-antigen release with the potential to disrupt the autoimmunity cycle and NET mediated tissue damage due to release of histone and other toxic NET components.
CIT-013 has a number of life cycle opportunities and after careful analysis we have chosen SLE as the first indication for which Citryll intends to obtain clinical Proof of Concept that CIT-013 can inhibit NET formation and promote NET clearance through NET and SLE biomarkers as well as exploratory clinical efficacy readouts.
A SAD study for determining Safety, tolerance and PK will be followed by a PD study consisting of a LPS nano-dosing challenge study to determine PD activity of CIT-013 in human subjects. This will be followed by a MAD study in SLE patients.