Our Science
Our Discovery Platform
Comprised of decades of experience designing optimized kinase inhibitors combined with computational chemistry resulting in a portfolio of over 400 unique compounds across multiple chemical series with associated structure-activity relationship data. These inhibitors have a variety of mechanisms of action that are potentially beneficial in a broad range of diseases as well as different pharmacokinetic activities allowing some compounds to be liver selective, others to be CNS penetrant or systemic.
Kinase Inhibitors in Liver Diseases
SRT-015 is a second-generation ASK1 inhibitor with an improved safety profile. SRT-015 has been specifically designed for treating liver diseases. SRT-015 has a trimodal therapeutic mechanism with demonstrated direct antifibrotic, anti-inflammatory, and anti-apoptotic activities in vitro and in vivo.
SRT-015 has shown an excellent efficacy in multiple preclinical models of acute and chronic liver injury. SRT-015 has completed phase 1 clinical trial (NCT04887038) in healthy volunteers, achieving therapeutically relevant exposure with an excellent safety and tolerability profile.
Dual kinase inhibitors in Central Nervous System Diseases
SRT-055 is representative of a first-in-class CNS-penetrant, dual LRRK2/ASK1 inhibitor series designed to treat diseases of the central nervous system, including Parkinson's. The LRRK2 kinase is a promising disease-modification kinase target with a genetic connection to Parkinson's disease. Mutations in LRRK2 that are associated with aberrantly enhanced kinase activity are the most common cause of genetic Parkinson's disease (10% of cases). New evidence suggests elevated LRRK2 kinase activity without LRRK2 mutations in idiopathic forms of the disease. Lysosomal dysfunction is a central pathology of Parkinson’s disease. Excessive LRRK2 activity results in lysosomal dysfunction that results in the accumulation of toxic products that cause cell damage.
Dopaminergic neurons are highly vulnerable to oxidative stress, activated LRRK2 kinase activity, and lysosomal dysfunction, all of which have critical roles in Parkinson’s disease. ASK1, present in all cells, is also activated by oxidative stress. The inhibition of ASK1 has demonstrated enhanced neuronal cell survival by inhibiting apoptosis and decreased inflammation by inhibition of activated CNS immune cells.
Dual inhibition of LRRK2/ASK1 could result in greater efficacy than LRRK2 inhibitors alone, and could allow treatment of a broader patient population, including those with identified LRRK2 mutations as well as patients with non-mutated LRRK2. This has the potential to produce a superior therapeutic for a larger population of Parkinson’s disease patients.
