Foresee Pharmaceuticals has announced positive preliminary results from its Phase 1 clinical trial of linvemastat (FP-020), a novel, highly selective, oral small-molecule matrix metalloproteinase-12 (MMP-12) inhibitor. The study, conducted in Australia, evaluated the safety, tolerability, and pharmacokinetics of oral ascending doses of linvemastat in healthy subjects.
The Phase 1 trial consisted of two parts: a single ascending dose (SAD) study involving 40 subjects and a multiple ascending dose (MAD) study with 24 subjects receiving once-daily oral doses of linvemastat or placebo for 10 days.
Safety and Tolerability
According to Dr. Yisheng Lee, Chief Medical Officer of Foresee, the overall safety profile of linvemastat in healthy volunteers was promising. The drug was well-tolerated, with no serious adverse events reported. The most common treatment-emergent adverse events (TEAEs) were mild nausea and headache, which were recoverable by the end of the study.
Potential in Immune-Fibrotic Diseases
Dr. Wenjin Yang, Chief Scientific Officer of Foresee, highlighted the unique product profile of linvemastat, noting its superior potency and pharmacokinetic properties compared to other MMP-12 inhibitors. The Phase 1 data supports the evaluation of different dosing intervals for daily administration in upcoming Phase 2 clinical trials.
Bassem Elmankabadi, M.D., Senior Vice President of Clinical Development of Foresee, stated that linvemastat holds great therapeutic potential as a disease-modifying oral therapy for severe asthma, chronic obstructive pulmonary disease (COPD), and inflammatory bowel diseases (IBD). This potential is based on the role of MMP-12 in modulating immune pathways and fibrosis in respiratory diseases and IBD, where significant unmet medical needs persist. The company plans to initiate Phase 2 studies in asthma and IBD in 2025.
About Linvemastat (FP-020) and MMP-12
Linvemastat (FP-020) is a highly potent and selective oral MMP-12 inhibitor targeting inflammatory and fibrotic diseases. It is the new-generation MMP-12 inhibitor developed by Foresee following aderamastat (FP-025), exhibiting greater potency and high selectivity. MMP-12 plays a key role in asthma pathophysiology and is associated with disease severity. MMP-12 is secreted by macrophages and regulates macrophage, neutrophil, and lung epithelial cell biology, making it a key marker of inflammatory exacerbations and fibrosis.
Foresee's Broader Pipeline
Foresee Pharmaceuticals is also developing aderamastat (FP-025), another oral MMP-12 inhibitor, which has shown positive outcomes in a Phase 2 proof-of-concept study in allergic asthmatic patients. Additionally, Mirivadelgat (FP-045), a highly selective oral small molecule allosteric activator of ALDH2, is undergoing clinical trials for Fanconi Anemia and is planned for pulmonary hypertension-interstitial lung disease (PH-ILD).
