Autoimmunity and Cathepsin S
Autoimmune diseases are characterized by an overactive response to the bodies own cells resulting in an inappropriate and uncontrolled activation of inflammatory pathways. This can result in serious tissue damage with pain and discomfort. Examples of autoimmune diseases include rheumatoid arthritis, psoriasis, psoriatic arthritis, multiple sclerosis, type I diabetes and numerous other indications.
General information on Autoimmunity: link here
Search MEROPS peptidase database: link to MEROPS here
Cathepsin S is expressed in a host of antigen presenting immune cells and plays a pivotal role in the major histocompatibility complex-II dependent presentation of self-antigens to T-cells, in particular autoreactive CD4+ cells. Selective modulation of cellular cathepsin S activity may provide a novel treatment for autoimmune diseases by blocking the processing of self-antigens and in turn inhibiting the activation of the T-cell and subsequent activation of inflammatory pathways.
Amura has developed low nanomolar inhibitors of cathepsin S with excellent selectivity against other cathepsins and attractive drug-like properties, with AM-3840 identified as the development candidate. In an in vivo collagen-induced arthritis study, our leading inhibitors demonstrated a marked reduction in collagen-specific antibodies, a significant decrease in joint swelling score and a significant improvement in joint histopathology.
Our leading inhibitors also have potential for use in psoriasis and multiple sclerosis.
In addition to this in vivo PoC data, the quality of the molecules is confirmed by a comprehensive pre-clinical package which includes pharmacokinetic data, selectivity and safety assessment. The lead molecule and a first rate back-up molecule are now available for partnering.
These drugs are the product of Amura’s AMcore™ platform which has reproducibly provided ‘fast-on, slow-off rate’ enzyme inhibitors with good pharmacokinetic half-lives and a very strong IP position.
Full Compound Information Summaries are available under Confidentiality Agreement.
Amura has licensing opportunities for its AMcore™-based programmes.