FP-025 (aderamastat) is a highly selective (non-hydroxamate), oral non-competitive small molecule inhibitor of Matrix Metalloproteinase-12/Macrophage elastase (MMP-12). This enzyme is a crucial mediator of matrix degradation and remodeling in both normal development and maintenance.

The Phase 1 human clinical trial was completed in December 2017. It was safe and well tolerated, and the pharmacokinetic profiles were in line with expectations. For detailed Phase 1 studies design, please visit：

• Single ascending dose (SAD):
  https://clinicaltrials.gov/ct2/show/NCT02238834?term=FP-025&rank=1
  (Identifier：NCT02238834)
• Multiple ascending dose (MAD):
  https://clinicaltrials.gov/ct2/show/NCT03304964?term=FP-025&rank=2
  (Identifier：NCT03304964)

The Phase 2 proof-of-concept study in allergic asthmatic patients in the Netherlands has been completed with positive outcomes announced in April 2023. For detailed design of the study, please visit：

• https://clinicaltrials.gov/ct2/show/NCT03858686?term=FP-025&rank=1
  (Identifier: NCT03858686)

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Sarcoidosis

Sarcoidosis is an inflammatory disease that affects one or more organs, most commonly the lungs and lymph glands. As a result of inflammation, abnormal lumps or nodules (called granulomas) develop in one or more organs of the body. These granulomas may alter the normal structure and function of the affected organ. 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. There are approximately 35,000 patients diagnosed each year in the United States, yet it remains underdiagnosed. Looking at the various forms of sarcoidosis, 5%~30% of sarcoidosis patients manifest cardiac engagement, additionally, sarcoidosis is the cause of 30% of interstitial lung diseases.

The pathogenesis of sarcoidosis is complex and unclear, and there are currently no targeted pharmaceutical treatments for cardiac sarcoidosis. Available treatments with limited benefits remain high dose steroids and cardiac medical devices. With no good treatments available for patients with steroid-unresponsive disease, which represents 30% of treated patients, there is clear medical need for new treatment options. Additionally, there is an opportunity for a new treatment like aderamastat to also help reduce steroid use in response patients. Based on the unmet needs, epidemiological data and market access considerations, this represents a potential commercial opportunity beyond US$1 billlion for aderamastat, not counting pulmonary sarcoidosis or other forms of the disease.

In patients with sarcoidosis, the MMP-12 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-025 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 has potential to effectively reduce the occurrence of side effects, most importantly, likely through a disease-modifying therapeutic effect.