- Inhibiting MMP-12 with FP-020 attenuated macrophage infiltration, macrophage clustering, decreased fibrotic replacement, and reduced the number of activated fibroblasts.
- Mice with a conditional deletion of the Tsc2 gene in CD11c+ cells leading to chronic activation of mTORC1 signaling in myeloid cells, caused spontaneous cardiac sarcoid-like granulomas.
- MMP-12 might therefore be required for granuloma formation and persistence, and further implicates a role of MMP-12 in cardiac fibrosis.
- The role of MMP-12 and its therapeutic implications may extend to other aspects of sarcoidosis and interstitial lung diseases.
TAIPEI, June 21, 2023 /PRNewswire/ -- Foresee Pharmaceuticals (6576.TWO), ("Foresee") announced today that the company and its collaborators presented a poster at the WASOG 2023 International Conference on Sarcoidosis and Interstitial Lung Diseases (ILDs), taking place June 19-21, 2023 in Stockholm, Sweden.
The poster entitled: "THERAPEUTIC EFFECT OF A NOVEL MMP-12 INHIBITOR IN A CARDIAC SARCOIDOSIS MOUSE MODEL" is the result of a collaboration between Foresee, the laboratory of Dr. Thomas Weichhart at the Center for Pathobiochemistry and Genetics, Medical University of Vienna, Austria, and Dr. Daniel Culver, the President of WASOG and the Chair of Department of Pulmonary Medicine at the Cleveland Clinic, Cleveland, OH, United States.
"We are very enthusiastic about the data in this poster, as it strongly validates MMP-12 as a potential target for cardiac sarcoidosis and strongly corroborates the evidence amassed to date, both by our group and collaborators, supporting a potentially pivotal role of MMP-12 biology in the pathophysiology of sarcoidosis and other diseases with immune-fibrotic and granulomatous components". "FP-020 is one of the most efficacious drugs we have tested in our sarcoidosis disease models", said Dr. Weichhart.
Additionally, Dr. Culver stated: "When putting in perspective this new exciting data where we observe a therapeutic benefit from FP-020 across multiple underlying components of the disease, both immune and fibrotic, and combining it with the existing body of non-clinical data as well as human expression data showing that MMP-12 is one of the most overexpressed protein in sarcoidosis patients, we remain very enthusiastic about the promise of Foresee's MMP-12 inhibitors as a potential unique treatment approach for sarcoidosis and ILDs.
Key Highlights from the Poster
- Sarcoidosis is an inflammatory, granulomatous disease of unknown etiology affecting multiple organs including the heart.
- Matrix Metalloproteinase-12 (MMP-12) degrades extracellular matrix and enables granuloma persistence and integrity.
- Here we assessed the effects of the selective MMP-12-inhibitor FP-020 in a cardiac sarcoidosis mouse model, where chronic activation of mTORC1 signaling in myeloid cells causes spontaneous cardiac sarcoid-like granulomas.
- Mice with the conditional deletion of the tuberous sclerosis 2 gene in CD11c+cells (Tsc2fl/flCD11ccre/+) were treated with the MMP-12-inhibitor FP-020 (30mg/kg/d) or with vehicle.
- Phenotypic changes in the heart between groups were evaluated by histological and immunological stains for markers of myeloid infiltration and fibrosis.
- The FP-020 treated groups showed significant histological improvements.
- Inhibition of MMP-12 led to a reduction of macrophage infiltrations, granuloma numbers, and cell clustering.
- Fibrotic collagen deposition was significantly reduced, as well as the total number of activated fibroblasts in the whole heart.
Poster Talk Session: Session 2, Tuesday June 20
Time: 15:32 CET
Location: Aula Medica, Stockholm, Floor 2
Poster number: 4998-A-2326
(https://mkon.nu/wasog2023/poster_talks_sessions)
The poster is available at Foresee's corporate website: https://www.foreseepharma.com/en-us/event/20
About Foresee Pharmaceuticals Co., Ltd.
Foresee is a Taiwan and US-based biopharmaceutical company listed on the Taipei Exchange (6576.TWO). Foresee's R&D efforts are focused in two key areas, namely its unique stabilized injectable formulation (SIF) long-acting injectable technology with derived drug products targeting specialty markets and secondly, its transformative preclinical and clinical first-in-class NCE programs targeting rare and severe disease areas with high unmet needs.
Foresee's product portfolio includes late and early-stage programs. CAMCEVI® 42 mg, for the treatment of advanced prostate cancer, is now approved in the U.S., Canada, and EU, and launched in the U.S. in April, 2022. Additionally, U.S. and EU regulatory submissions are under preparation for CAMCEVI® 21 mg, the U.S. regulatory submission is anticipated in 2024. The second indication of CAMCEVI® 42 mg- central precocious puberty (CPP), the phase 3 clinical study is currently being initiated. FP-025 - a highly selective oral MMP-12 inhibitor targeting inflammatory and fibrotic diseases, a Phase 2 proof-of-concept study in allergic asthmatic patients, the study has been completed with positive outcome. FP-045 - a highly selective oral small molecule allosteric activator of ALDH2, a mitochondrial enzyme, for which a Phase 1b/2 Fanconi Anemia study is currently being initiated, and a P2 study in pulmonary hypertension group 3 patients is in planning. www.foreseepharma.com
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