NCE Pipeline

MMP-12 inhibitors

MMP-12 (matrix metalloproteinase-12/macrophage metalloelastase) is a key regulator of tissue extracellular matrix and modulator of matrikine signaling. MMP-12, a key modulator of immune and fibrotic biology, is predominantly secreted by macrophages and is becoming recognized as a key marker of inflammatory exacerbations and fibrosis. MMP-12's key role in disease is supported by genetic/GWAS evidence related to inflammatory-fibrotic diseases across multiple target tissues, namely the lung, heart and kidney.

FP-025 (aderamastat) is a first-in-class highly selective oral MMP-12 inhibitor targeting inflammatory and fibrotic diseases. Following the successful completion of a Phase 2 proof-of-concept study in allergic asthmatic patients in 2023, a remarkable accomplishment as Foresee was the first company to validate the biological potential of MMP-12 as a therapeutic target in humans. The body of data now paints a full biological story for MMP-12 as a human therapeutic target, from human genetic data, through human expression data in various disease states (including asthma and sarcoidosis patients), genetic models of diseases and now in a promising Phase 2 allergic asthma PoC study. Foresee has decided to focus aderamastat’s future development in rare immune-fibrotic diseases, including cardiac sarcoidosis on the basis of compelling translational data.

In addition to aderamastat, Foresee has nominated a follow-on MMP-12 inhibitor Development Candidate, FP-020 (linvemastat), which are currently in Phase 1 studies in preparation for P2 studies targeted in severe asthma, COPD and IBD in 2025.

On the basis of the aderamastat P2 data, Foresee is the first company to demonstrate the therapeutic value of MMP-12 as a biological target.

Foresee’s diverse set of clinical and development candidates with distinct profiles as well as distinct patent estates will allow us to maximize the value of MMP-12 as a target for the treatment of multiple unmet severe diseases, both rare and common.

ALDH2 activators

ALDH2 (Aldehyde Dehydrogenase 2) is a mitochondrial matrix enzyme and key regulator of mitochondrial quality control systems/health and regulator of reactive aldehydes/carbonyls, oxidative stress, inflammation, and fibrosis. Activation of ALDH2 is a compelling therapeutic strategy for improving mitochondrial quality and regulatory mechanisms for the treatment of rare/orphan diseases and severe diseases of aging, including diseases of the blood, kidney, muscles, nerves/brain, lung, and heart. The key role of ALDH2 in disease is supported by strong genetic/GWAS evidence related to a dominant-negative ALDH2*2 polymorphism.

FP-045 (mirivadelgat) is a highly selective oral small molecule allosteric activator of ALDH2. FP-045 pediatric formulation has successfully completed single and multiple ascending dose Phase 1 studies, a 28-day repeat dose Phase 1 study, and 3-month GLP toxicology studies. Foresee has initiated a P1b/2 PoC study in Fanconi Anemia patients in 2023 and seeking to expand the PoC strategy to other rare/orphan and severe pediatric diseases.

Foresee is planning to initiate a Phase 2 study testing a solid oral dosage of FP-045 in pulmonary hypertension associated with interstitial lung diseases (PH-ILD) patients in 2024. There is compelling biology supporting the role of ALDH2 activation as a unique therapeutic approach for PH that may be, based on preclinical data, disease-modifying via improvement of lung (interstitial fibrosis), heart and pulmonary artery function.

In addition to FP-045, Foresee has also identified follow-on compounds of oral ALDH2 activators currently in late preclinical stage, as a target for the treatment of CVRM diseases and neurology.

Below is a schematic highlighting the potential role of ALDH2 and Foresee’s oral ALDH2 activators in the treatment of rare and chronic severe diseases including CVRM: