FP-020 (linvemastat): Asthma; COPD; IBD

FP-020 (linvemastat) is a new-generation, best-in-class, oral MMP-12 inhibitor developed by Foresee, with a distinct product profile from FP-025 (aderamastat). Differentiating features include once-a-day oral dosing (vs twice-a-day for aderamastat), more potent inhibition of MMP-12, and importantly a distinct patent series with very long composition of matter exclusivity protection. Linvemastat is currently being tested in Phase 1 SAD/MAD healthy volunteer studies and initiating supporting chronic GLP toxicology studies, with the objective of initiating Phase 2 studies in both asthma and IBD in 2025. Linvemastat represents a unique “pipeline-in-a-product” opportunity that has the potential to capture multibillion US dollar markets as it becomes an anchor product across the immune-fibrotic disease segment and beyond.

The Phase 1 SAD/ MAD studies evaluating FP-025 in healthy volunteers are ongoing. For detailed Phase 1 studies design, please visit:https://clinicaltrials.gov/study/NCT06334211

 

Asthma

Asthma is a chronic respiratory condition characterized by recurrent wheezing, coughing, and breathlessness, which occur in acute events known as exacerbations. There are multiple phenotypes and endotypes of asthma with multiple pathophysiological processes. Endotypes include Type 2 (characterized by high Th2 cell populations), and non-Type 2 (often characterized by low eosinophil counts).

Inhaled corticosteroids (ICS) and long-acting beta-adrenergic agonist (LABA) combinations are the baseline standard of care. ICS/LABA/long-acting muscarinic agonist (LAMA) triple combinations are expected to capture a larger share of the severe asthma treatment market. Novel severe asthma biologics (e.g., IL-5, IL4/IL-13, TSLP-1 pathway injectable biologic modulators) have demonstrated significant success as add-ons to inhaled standard care.

However, there remains a very high unmet need for new mechanisms that can complement current treatments, particularly oral drugs that can improve compliance in the pre-biologic patient segment, where inhaled therapies have poor compliance. Additionally, oral drugs that can provide added benefit in the broader phenotypes and difficult to treat asthma groups, including demonstration of reduction in exacerbations, improvement in lung function, and reduction in corticosteroid use.

Building on the success of Foresee’s FP-025 (aderamastat) Phase 2 proof-of-concept and years of MMP-12 translational biology, linvemastat was developed as an ideal candidate for asthma populations.

Given the unmet needs, market dynamics, and strong demand for oral drugs with new mechanisms, FP-020 (linvemastat) is expected to achieve blockbuster status post-launch.

Chronic Obstructive Pulmonary Disease (COPD)

COPD is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. Symptoms include breathing difficulty, cough, mucus production, and wheezing.

COPD patients are at higher risk of developing heart disease, lung cancer, and other diseases. According to Datamonitor Healthcare, in 2023, there were approximately 319.7 million COPD cases worldwide, projected to increase to 328.9 million prevalent cases by 2027. According to the World Health Organization, COPD is the third leading cause of death globally.

The current baseline standard of care of COPD consists of multiple inhaled combinations of ICS, and both long and short-acting beta-adrenergic and muscarinic receptor agonists (SABA, LABA, SAMA, LAMA). Few add-on treatments are available such as PDE-4 inhibitors.

A compelling body of translational data supports a key role for MMP-12 in COPD disease biology and the potential of MMP-12 inhibitors as a new treatment modality. Depending on the severity of airflow limitation, MMP-12 mRNA levels were significantly elevated in COPD patients (severe and very severe). Serum MMP-12 concentration of COPD patients was directly related to COPD severity.

Given the strong unmet need for new oral add-on treatments with disease-modifying potential, Foresee has strong conviction in the potential linvemastat for the treatment of COPD.

Inflammatory Bowel Diseases (IBD)

IBD describes disorders chronic inflammation of tissues of the digestive tract. IBD falls into two categories:

  • Ulcerative colitis (UC): Involves inflammation and ulceration along the lining of the colon and rectum.
  • Crohn's disease (CD): Characterized by inflammation of the digestive tract lining, often including deeper layers.

According to Datamonitor Healthcare, there was an estimated 11.3 and 6.3 million cases of UC and CD respectively worldwide in 2023, expected to increase to 13.5 and 6.5 million cases respectively by 2027. An estimated 30% or more of IBD patients remain untreated. Treated patients experience high rates of non-response and secondary loss of response, with a 30-50% failure rate.

The current commercial IBD opportunity is very significant with combined sales of biologics and targeted small molecules in CD and UC which projected to exceed US$22 billion in 2024 and US$34 billion in 2032. There remains a great need for new oral treatments with novel mechanisms with stronger efficacy, better safety, and the potential to target treatment failure/resistant patients.

Foresee has identified a unique opportunity for FP-020 (linvemastat) to become a first-in-class oral treatment for IBD addressing key unmet need in therapy resistance and fibrosis.

As literature supports, MMP-12 expression is strongly associated with the severity of IBD and the response to biological therapies. Foresee's non-clinical animal pharmacology studies in humanized IBD models demonstrated linvemastat's superior activity to Humira as a single agent and additive combination efficacy. Foresee sees a strong opportunity for linvemastat to become a first-in-class oral therapy and leader in the space of IBD.