FP-020: Sarcoidosis, Idiopathic pulmonary fibrosis (IPF), emphysema
The FP-020 series of compounds are the new-generation MMP-12 inhibitors developed by the Foresee following FP-025, with oral higher potency and similar high selectivity. They have shown excellent results in idiopathic pulmonary fibrosis, Interstitial lung disease, and Sarcoidosis animal models. Patent applications have been filed with the U.S. Patent and Trademark Office, and strategies for clinical development are being evaluated.
The FP-020 series of compounds via the specific MMP-12 inhibition mechanism has potent effects in the animal model; therefore, FP-020 can potentially emerge as an alternative therapeutic drug to target these indications.
Sarcoidosis is a multisystem granulomatous disease that primarily affecting the lungs, skin, liver, and thoracic lymph nodes. Chronic pulmonary sarcoidosis causes irreversible lung damage and a shorter life expectancy. Sarcoidosis is uncommon, with a prevalence of about 1-40 per 100,000 people. There are approximately 185,000 cases of sarcoidosis in the United States and about 1.2 million worldwide. The pathogenesis of sarcoidosis is complex and unclear, and there are currently no preventive strategies for sarcoidosis. The current use of glucocorticoids as the primary treatment has mixed results and is associated with serious adverse effects.
In patients with sarcoidosis, the MMP12 gene is highly expressed in areas of active granulomatous inflammation; targeting MMP-12 might be a novel approach to granuloma resolution in pulmonary sarcoidosis. The ability of FP-020 to inhibit the expression and activity of MMP-12 will help to inhibit the occurrence and formation of granulomas in sarcoidosis, and it has strong specificity and will not inhibit other MMPs. It is expected to reduce the occurrence of side effects .
Once FP-020 is developed into a potential therapy, the therapeutic effect may benefit sarcoidosis patients.
Idiopathic pulmonary fibrosis (IPF)
Idiopathic pulmonary fibrosis (IPF) is a severe but rare lung disease lung disease characterized by chronic interstitial pneumonia and progressive deposition of fibrotic tissue in the lungs, with symptoms including dyspnea, cough, and poor quality of life, advance progression, and death. According to the National Institutes of Health (NIH), about 100,000 people in the United States have IPF. Approximately 30,000 to 40,000 new cases are diagnosed each year. Worldwide, IPF affects 13 to 20 out of every 100,000 people.
Acute exacerbation of idiopathic pulmonary fibrosis remains an unmet medical need. All patients require supportive care to relieve hypoxemia and alleviate symptoms of shortness of breath and cough. Most experts administer systemic glucocorticoids, although randomized trial data are lacking. Broad-spectrum antibiotics are typically initiated as the radiographic findings presented with pneumonia. Accumulating data suggest that the antifibrotic agents help prevent AEs. Unfortunately, the value of adding or continuing antifibrotic agents during an AE remains unknown.
Pulmonary emphysema, a progressive lung disease, is a form of chronic obstructive pulmonary disease (COPD). It is characterized by abnormal permanent enlargement of lung air spaces with the destruction of their walls without any fibrosis and destruction of lung parenchyma with loss of elasticity. This may be due to some internal or external factors that lead to long-term inflammation of the alveolar outer membrane and result in permanent damage to the alveolar structure. In such damaged alveoli, the efficiency of gas exchange is very poor, resulting in insufficient oxygen and carbon dioxide retention in the body, which seriously affects the patient's mobility and normal life. Chronic bronchitis, bronchial asthma, silicosis, and tuberculosis can cause this disease, but the main risk factor is smoking; common symptoms are cough, phlegm, shortness of breath, cyanosis, etc. The long-term development of the disease can lead to pulmonary heart disease.
The prevalence of emphysema in the United States is approximately 14 million. Currently, no known, definitive treatment can modify the disease process. Medical therapy includes using a bronchodilator alone or with anti-inflammatory drugs such as corticosteroids and phosphodiesterase-4 inhibitors.
Inflammatory Bowel Disease (IBD)
Inflammatory bowel disease (IBD) is characterized by repetitive episodes of inflammation of the gastrointestinal tract caused by an abnormal immune response to gut microflora. Inflammatory bowel disease encompasses two types of idiopathic intestinal disease that are differentiated by their location and depth of involvement in the bowel wall. Ulcerative colitis (UC) involves diffuse inflammation of the colonic mucosa. Most often, UC affects the rectum (proctitis). Still, it may extend into the sigmoid (proctosigmoiditis), beyond the sigmoid (distal ulcerative colitis), or include the entire colon up to the cecum (pancolitis). Crohn’s disease (CD) results in transmural ulceration of any portion of the gastrointestinal tract (GI), most often affecting the terminal ileum and colon. Both diseases are classified by extent (mild, moderate, or severe) and location. The CD also is classified by phenotype- inflammatory, structuring, or penetrating.
Besides the GI tract, Crohn’s disease and ulcerative colitis have many extraintestinal manifestations. While the disorders can be distinguished in most patients, the features are so similar in at least 10% of patients that it is impossible to differentiate between them initially.
Both disorders have a genetic predisposition; neither is curable and carries enormous morbidity. Finally, both increase the risk of colorectal cancer.
Foresee is planning to advance one of the MMP-12 inhibitors (FP-020 or FP-025) to the IBD clinics in the near future, and will be announced accordingly.