Foresee is developing a new-generation, novel oral, high potency, highly selective and non-hydroxamate-based matrix metalloproteinase-12 (MMP-12) inhibitors based on rational drug design. The increase of the proteolytic enzyme MMP-12 is implicated in many diseases, such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), acute lung injury (ALI), sarcoidosis, Alport syndrome (rare genetic kidney disease), atherosclerosis, ischemic retinopathy, wound healing, multiple sclerosis, cystic fibrosis, osteoarthritis, rheumatoid arthritis, allergic rhinitis, inflammatory bowel Disease (ulcerative colitis and Crohn’s disease), nephritis and tumor growth (lung cancer metastasis). Therefore, Foresee’s small molecule MMP-12 inhibitors have the potential to treat these diseases.
A lead compound, FP-025, the Phase 1 human clinical trials has been completed and proved to show acceptable safety and tolerability, and stable pharmacokinetics in healthy subjects. A Phase 2 proof-of-concept study in allergic asthma patients is currerently undergoing in the Netherlands, and has expanded into the research of COVID-19 associated ARDS in a Phase 2/3 study. The Phase 2 study was terminated, and the results are anticipated in 2H2022. A follow-on compound FP-020, a highly selective MMP-12 inhibitor, has also been identified and will be used to explore other potential indications such as idiopathic pulmonary fibrosis (IPF), sarcoidosis and emphysema.
Aldehyde Dehydrogenase 2 (ALDH 2) is a key mitochondrial regulator of toxic aldehyde metabolism. Those toxic aldehydes are associated with many mitochondrial-mediated cardiovascular-metabolic diseases (PAD, diabetes, NAFLD/NASH, heart failure, etc.) and rare diseases (Fanconi Anemia, Parkinson's disease, Shwachman-Diamond Syndrome, Ataxia etc.).
Foresee licensed in a clinical stage compound and the platform technology of ALDH 2 from US-based Aviv Therapeutics, Inc. A lead compound, FP-045, is a novel, potent, oral small-molecule ALDH2 activator. Activation of ALDH2 by its agonist can potentially accelerate toxic aldehyde metabolism and can theoretically provide the treatment of these diseases. FP-045, the Phase 1 human clinical trials has been completed and proved to show acceptable safety and tolerability, and stable pharmacokinetics in healthy subjects. A Phase 2 proof-of-concept study in fanconi anemia patients is currerently being initiated. A follow-on compound FP-040, has also been identified and will be used to explore other potential indications such as central nervous system (CNS) diseases.