MMP-12 inhibitor

Foresee is developing new-generation, novel oral, high potency, highly selective, non-hydroxamate-based matrix metalloproteinase-12 (MMP-12) inhibitor, potentially having therapeutic effects across several diseases.

The increase of the proteolytic enzyme MMP-12 manifested 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 (IBD) (e.g., ulcerative colitis (UC) and Crohn’s disease (CD)), interstitial nephritis, and tumor growth (lung cancer metastasis). Based on the scientific rationale and chemical structure of the (MMP-12) inhibitor drug, it could have therapeutic effects on these diseases.

A lead compound, Aderamastat (FP-025), was studied in several clinical trials, including a Phase 1 healthy volunteers study that showed an acceptable safety and tolerability profile with stable drug pharmacokinetics. 

In addition to the Phase 1 studies, Foresee completed a Phase 2 trial in adult patients with severe to critical COVID-19 with associated Acute Respiratory Distress Syndrome (ARDS). The topline results of the study were announced on August 3, 2022, although the primary endpoint was not statistical significance; Foresee conducted further analysis of biomarker data, which showed promising effects that Aderamastat (FP-025) could be beneficial in more severe patients’ population.

For Foresee to build on the proof of concept of MMP-12, Aderamastat (FP-025) was tested in a Phase 2 study in allergic asthmatic patients with blood eosinophilia. Recently the study was completed, and the topline results of the primary endpoint analysis of Late Asthmatic Response (LAR) were positive and announced on April 4, 2023., additional secondary endpoints, such as biomarker analysis, is planned to be disclosed in the European Respiratory Society (ERS) Congress in Milan, Italy, in September 2023. Follow-on compound (FP-020), a highly selective MMP-12 inhibitor, and that will be used to explore other potential indications such as idiopathic pulmonary fibrosis (IPF), sarcoidosis, and emphysema.

ALDH2 activator

Aldehyde Dehydrogenase 2 (ALDH 2) is a critical 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 accelerate toxic aldehyde metabolism and can theoretically provide the treatment of several diseases like Fanconi Anemia (FA) and Pulmonary arterial hypertension (PAH). FP-045, was tested in a Phase 1 healthy volunteers studies that have been completed and showed acceptable safety, tolerability, and stable pharmacokinetics. A Phase 2 proof-of-concept study in Fanconi Anemia patients is currently being initiated. Foresee also identified a follow-on compound (FP-040), and that will be used to explore other potential indications, related to central nervous system (CNS) diseases.