Foresee Pharmaceuticals has announced the dosing of the first patient in its Phase 2 WINDWARD study, evaluating mirivadelgat (FP-045) for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD). This milestone marks a significant step forward in addressing an underserved patient population with limited therapeutic options.
The WINDWARD study is designed as a multinational, double-blind, three-arm trial that will evaluate the safety and efficacy of mirivadelgat, an oral aldehyde dehydrogenase 2 (ALDH2) activator, in adult patients aged 18 to 85 years with PH-ILD. The 16-week study will enroll 99 patients, with 33 evaluable subjects in each cohort.
Trial Design and Endpoints
The primary endpoint of the WINDWARD study will measure the mean change from baseline to week 12 in pulmonary vascular resistance (PVR), assessed by right heart catheterization, comparing mirivadelgat versus placebo. The trial will also evaluate multiple secondary endpoints, including changes in long-term prognostic risk factors such as N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels and functional capacity measured by the 6-minute walk distance test.
"Dosing of the first patient in the WINDWARD study is a testament to the dedication of our team to finding a potential therapy for patients with PH-ILD," stated Bassem Elmankabadi, M.D., Senior Vice President of Clinical Development at Foresee Pharmaceuticals. "This trial builds on rigorous foundations and incorporates a robust design to evaluate mirivadelgat's safety and efficacy across several clinical endpoints, including improvements in peripheral vascular resistance and functional capacities in PH-ILD patients."
Novel Mechanism of Action
Mirivadelgat represents a scientific breakthrough as the first oral ALDH2 activator in clinical development for PH-ILD. Preclinical studies have demonstrated promising disease-modifying activity, affecting both the cardiovascular and pulmonary components of the condition.
Dr. Wenjin Yang, Ph.D., Chief Scientific Officer at Foresee, highlighted the drug's potential: "Mirivadelgat is a scientific breakthrough mechanism targeting ALDH2 activation. Preclinical data demonstrated mirivadelgat's disease modifying activity on lung fibrosis, heart hypertrophy, and fibrosis as well as pulmonary and cardiac function. The WINDWARD trial will validate its clinical impact, potentially ushering in a new treatment era for patients with limited options."
Addressing a Significant Unmet Need
PH-ILD represents a complex and devastating condition characterized by abnormally high mean pulmonary arterial pressure due to progressive vasoconstriction and vascular remodeling of the distal pulmonary arteries. Approximately 30% of patients with interstitial lung disease develop pulmonary hypertension, with estimates suggesting up to 100,000 diagnosed PH-ILD patients in the United States alone.
The condition can develop in patients with various forms of interstitial lung disease, including idiopathic pulmonary fibrosis (IPF), pulmonary fibrosis (PF), combined pulmonary fibrosis and emphysema (CPFE), and connective tissue disease (CTD). Currently, inhaled treprostinil is the only approved treatment for PH-ILD, highlighting the significant unmet need for additional therapeutic options.
Dr. Ben Chien, Ph.D., Chairman and CEO of Foresee Pharmaceuticals, emphasized the significance of this milestone: "Today's achievement reflects Foresee's unwavering mission to pioneer life-changing therapies. The initiation of Phase 2 for mirivadelgat is a strategic milestone that brings us closer to delivering hope to millions affected by the PH-ILD condition."
Potential for Broader Applications
Foresee is positioning mirivadelgat as a first-in-class, once-daily oral drug not only for PH-ILD but potentially for other rare and severe diseases. The company's ALDH2 activators have shown compelling non-clinical efficacy across multiple animal pharmacology and translational models, highlighting the pivotal role of ALDH2 activation in modulating mitochondrial stress, energetics, tissue inflammation, fibrosis, and muscle function.
The efficacy observed in models of heart failure, pulmonary hypertension, muscle dysfunction, and pulmonary fibrosis/interstitial lung disease has been described as "highly impressive," demonstrating disease-modifying effects on lung fibrosis, heart hypertrophy and fibrosis, as well as pulmonary and cardiac function.
About Foresee Pharmaceuticals
Foresee Pharmaceuticals is a Taiwan and US-based biopharmaceutical company listed on the Taipei Exchange. The company's R&D efforts focus on two key areas: its unique Stabilized Injectable Formulation (SIF) long-acting injectable technology with derived drug products targeting specialty markets, and its transformative preclinical and clinical first-in-class novel chemical entities targeting rare and severe disease areas with high unmet needs.
The company's product portfolio includes both late and early-stage programs, including CAMCEVI 42 mg for advanced prostate cancer, which is already approved in multiple markets including the U.S., Canada, EU, Taiwan, Israel, and the UK. Foresee is also developing additional candidates including aderamastat (FP-025), a highly selective oral MMP-12 inhibitor, and linvemastat (FP-020), a follow-on oral MMP-12 inhibitor.
