Exclusive deal to develop and commercialise Amgen’s Phase 1 APJ agonist, after BioAge platform identifies its potential in promoting longevity and reducing symptoms of muscle aging.
Californian biotech BioAge Labs today announced an exclusive worldwide licence agreement with Amgen to develop and commercialise the biopharma giant’s clinical-stage APJ agonist to ameliorate muscle aging. BioAge, which develops treatments that target the molecular causes of age-related disease to extend healthy human life, is aiming for its first human trials early next year.
Longevity.Technology: Since securing a $90m Series C investment round, BioAge has started Phase 2 trials for its BGE-117 and BGE-175 compounds, and shows no sign of slowing down with this latest development. It’s easy to see why the company is interested in a drug with potential to treat muscle aging, which causes loss of strength, mobility, and function among older people, while driving mortality and multiple age-related diseases and decreasing overall quality of life.
BioAge has named the compound BGE-105 (originally named AMG 986 by Amgen), and secured the licence after its human-centric AI discovery platform revealed that the apelin–APJ pathway preserves muscle function in older people and predicts future longevity.
“BioAge’s advanced proprietary platform comprehensively analyses longitudinal human data to identify key molecular drivers of aging, which we then validate in preclinical experiments,” said BioAge co-founder and CEO, Dr Kristen Fortney.
“Using this robust approach, we found that higher levels of apelin signalling in older people are associated with increased lifespan and reduced symptoms of frailty. Our human-first analysis suggests that the apelin-mimicking drug BGE-105 could recapitulate these positive effects in older patients.”
Preclinical work shows positive results
APJ and its natural agonist apelin are components of a signalling pathway that regulates multiple aspects of muscle metabolism, growth and repair. In mice, deficiency in apelin or APJ accelerates loss of muscle function. BioAge showed in preclinical experiments that BGE-105 increases running wheel activity, improves regeneration, and decreases muscle atrophy due to immobilisation in old mice.
BioAge collaborated on this work with Dr Cedric Dray, an associate professor at French public health research organisation Inserm. In 2018, Dray’s research group discovered that apelin reverses age-associated sarcopenia, and he has since worked with BioAge to evaluate BGE-105 in murine models of muscle regeneration.
“Maintaining muscle mass and strength is key to maintaining physical function in the elderly,” said Dray. “It is tremendously exciting to trial in humans an oral APJ agonist that recapitulates the positive effects of apelin peptide.”
“Because it targets a fundamental mechanism of muscle aging, BGE-105 could be used to treat multiple acute and chronic indications, potentially improving muscle strength in frail elderly people, shortening rehabilitation time after hip fracture, or increasing mobility after extended bed rest,” added Fortney.
“The licensing agreement represents a major milestone toward our vision of developing a pipeline of treatments that separate growing older from disability and disease, dramatically improving the quality of life as we age.”
Human trials in 2022
BGE-105 is a potent APJ agonist that can be administered orally or intravenously. Phase 1 clinical trials completed by Amgen in 2019 showed that it had a tolerable safety profile. BioAge’s first clinical trial of BGE-105, planned for initiation in the first quarter of 2022 under the existing IND, will be a Phase 1 study comparing the pharmacodynamic effects of BGE-105 in humans with those of apelin peptide.
Fortney says that BGE-105 is de-risked in two key ways. “First, data from a previous clinical trial show that the molecule was well tolerated in human patients. Second, our human-centric approach reveals that the drug target is physiologically relevant to human aging – in this case, showing that enhancing apelin signalling is compatible with a long and healthy lifespan.”
Under the terms of the licence agreement, which covers all indications, BioAge will make an upfront payment to Amgen, which is entitled to receive development and regulatory milestone payments plus royalties based on annual net sales. Amgen will also receive BioAge shares. BioAge will be responsible for all development, manufacturing, and commercialisation of BGE-105 worldwide.