BGE-117: BIOAGE’S FIRST CLINICAL-STAGE ASSET TARGETS HIF SIGNALLING
A core longevity pathway that drives regeneration, healing, and resilience
The Hypoxia-inducible factor (HIF) pathway is linked to lifespan and healthspan in BioAge’s proprietary human aging data. Pathway activation levels are significantly associated with longevity and multiple functional measures. BGE-117 is a hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor that can potentially treat multiple diseases of aging through the activation of HIF-1 target genes that are involved in numerous biological processes including tissue regeneration, erythropoiesis, glycolysis, glucose uptake, vascular remodeling and angiogenesis.

The molecular pathways impacted by BGE-175 are linked to lifespan and healthspan in BioAge’s proprietary human aging data. The prostaglandin pathway, as well as several key components of the immune response to viral challenge, are significantly associated with longevity and multiple functional measures. Inhibition of PGD2 DP1 receptor signaling impacts multiple immune mechanisms, including activation of dendritic cells and NK cells, and reducing neutrophil infiltration. Preclinical studies demonstrate that BGE-175 inhibits neutrophil migration and that DP1 inhibition boosts dendritic cell function, both of which counteract known aspects of immune aging, and are also therapeutically promising for COVID-19 and other respiratory infections.

Apelin is a small secreted peptide hormone that regulates multiple aspects of muscle physiology, including cell growth and survival, regeneration, and repair. BioAge’s analysis of our proprietary longitudinal aging data revealed that higher apelin signaling activity correlates with improved muscle function, reduced frailty, and longer lifespan. Apelin levels decline with age, and activation of apelin signaling reverses age-related sarcopenia in mice. BGE-105, an oral agonist of the apelin receptor APJ, could ameliorate muscle aging, which causes loss of strength, mobility, and function, driving mortality and multiple age-related diseases. By targeting this fundamental mechanism of aging, BGE-105 could treat multiple acute and chronic indications: improving muscle strength in frail patients, accelerating rehabilitation following fractures, and increasing mobility after extended bed rest.