Small Molecule BTK Kinase Inhibitors

As part of a novel kinase inhibitor platform Aegera has identified a proprietary lead series of small molecule Btk kinase inhibitors. Btk (Bruton's tyrosine kinase) is a key non-receptor tyrosine kinases involved in immune cell signalling and function. Btk, a Tec family kinase, plays a pivotal role in the B Cell Receptor (BCR) signalling pathway and is critical for the development and activation of B lymphocytes. Btk inhibition holds great potential for the treatment of multiple autoimmune/inflammatory diseases and haematological/lymphoid malignancies. Compounds are being profiled in SAR assays looking at in vitro and cellular potency, PK, in vitro ADME, pharmacodynamics and efficacy in RA/autoimmune models, and will shortly be tested in cancer models. There is a continuing effort around medicinal chemistry optimization, leveraging information gathered from the various in vitro and in vivo profiling assays described above.

Small Molecule FMS (CSF-1R) Kinase Inhibitors

Aegera has identified a proprietary lead series of small molecule Fms kinase inhibitors. Fms is a transmembrane tyrosine kinase receptor for CSF-1, involved in macrophage survival and function as well as osteoclast formation. FMS inhibition holds great potential for the treatment of multiple autoimmune/inflammatory diseases and cancer.

Compounds are being profiled in SAR assays looking at in vitro and cellular potency, PK, in vitro ADME, pharmacodynamics and efficacy in xenograft models, and will also be tested in autoimmune disease models of RA and MS.

IAP Inhibitors for the Treatment of Autoimmune and Inflammatory Diseases

The Inhibitor of Apoptosis proteins (IAPs) are emerging as promising targets for autoimmune and inflammatory diseases. Data generated by Aegera demonstrate that IAPs play important roles in the modulation of key cell types which contribute to the pathophysiology of rheumatoid arthritis and that pharmacological inhibition of specific IAPs is a novel approach which may provide therapeutic benefit in autoimmune diseases such as RA. Aegera is currently exploring the use of its IAP inhibitors in non-oncology indications, and has generated very promising POC data in rodent models of rheumatoid arthritis. Aegera has identified early lead compounds and is currently exploring the path that would lead the identification/nomination of development candidate(s).

HSP90 Inhibitors

Aegera has identified novel and proprietary lead small molecule HSP90 inhibitors which have potential for the treatment of fungal infections, inflammation/autoimmune diseases, cancer and neurodegenerative diseases. Aegera has generated in vitro and in vivo data demonstrating that its HSP90 inhibitors can modulate key client proteins involved in the regulation of signalling pathways which play pivotal roles in inflammation, oncology and neurodegeneration at pharmacologically relevant concentrations.

Furthermore, Aegera HSP90 inhibitors sensitize pathogenic fungi to standard anti-fungals (azoles) and cause a switch from fungo-static to fungo-cical.