Humanised Neutralising Antibodies for the Treatment of Fibrotic Diseases
Fibrosis is an essential process that is a critical for wound healing. However, excessive and maladaptive fibrosis is common in many disease conditions and is an important disease mechanism. Diseases characterized by excessive fibrosis include rare genetically driven diseases such as systemic sclerosis, scleroderma, idiopathic pulmonary fibrosis, focal segmental fibrosis of the kidney and hypertrophic cardiomyopathy and common diseases such as atrial fibrillation, myocarditis, liver cirrhosis, glaucoma and diabetic kidney disease. Despite the large impact on human health, therapeutic approaches to prevent, limit or reverse fibrosis across tissues still represent an unmet medical need.
The best characterized target for fibrosis is TGFB1 but despite there being therapeutic antibodies against this target for many years (Genzyme, Sanofi) it has not progressed due to the multi-faceted effects of TGFB1 and the fibrosis-independent side effects (e.g. skin cancers, immune disorders) of inhibiting this upstream and multi-functional target.
The team’s approach gains superior specificity for targeting fibrosis by acting on a novel, presently not targeted molecule, downstream of TGFB1 and multiple other upstream pro-fibrotic stimuli thus avoiding redundancy. It inhibits a process very specific to the fibrotic disease, tailored to the key players of the fibrotic response: activated fibroblasts.
Fully human optimized therapeutic antibodies (leads) with improved affinity/on-off rate, solubility and half-life suited for rapid development as a new medical entity. Additionally, companion diagnostic assays that measure the genetic factors that predict the secretion of the identified molecule will be developed in parallel.
Principal Investigator: Professor Stuart Cook
Institution: National Heart Centre Singapore
NHIC Ref: NHIC-I2D-1604106