Kristen Fortney on the pathway to longevity

BioAge CEO discusses positive muscle atrophy clinical trial results and teases possible cognitive direction.

A couple of weeks ago we brought you the news that clinical stage biotech BioAge had announced positive topline results for its clinical trial evaluating muscle atrophy, the wasting or decrease in size of muscle tissue that can occur as a result of a variety of factors, including disuse, aging, malnutrition and certain medical conditions.

BioAge’s positive results news concerned its Phase 1b clinical data for BGE-105, a highly selective, potent, orally available small-molecule agonist of the apelin receptor APJ.

In the trial, treatment with BGE-105 resulted in statistically significant prevention of muscle atrophy relative to placebo in healthy volunteers aged 65 or older after 10 days of strict bed rest.

Longevity.Technology: Muscle atrophy is a universal feature of human aging that leads to a loss of strength and functional ability. Not only do weakened muscles make it difficult to perform everyday activities, muscle atrophy can also contribute to a decrease in metabolism, which can contribute to weight gain, other health problems and even disability.

Not only does this trial indicate that BGE-105 hold promise for use in hospitals and care facilities, but being able to prevent the loss of muscle strength and mass associated with aging – sarcopenia – could reduce the numbers suffering with frailty. Frailty is an age-related medical syndrome that correlates with adverse health outcomes such as death, hospitalisation and falls [1], so a compound that can bring about more favourable outcomes for those in danger of developing sarcopenia would be significant.

With this in mind, we were glad to follow up on BioAge’s BGE-105 news with its CEO and Founder, Dr Kristen Fortney; we asked her if BioAge is indeed eyeing a wider use to prevent age-related muscle frailty and guard against the dangers of frailty.

Dr Fortney told us that while ICU diaphragmatic atrophy and critical care myopathy have an enormous impact on health and affect millions of people, no therapies have been approved.

“This high unmet medical need makes these conditions important first indications for BGE-105,” she explains. “And over the course of our Phase 2 trial for acute myopathies, we’ll learn a great deal about the impact of BGE-105 on peripheral muscles, informing further clinical development.

“Loss of muscle mass and strength is a nearly universal aspect of growing older, so over the longer term, we’re excited by the potential for correcting dysregulation of apelin signaling to treat or prevent conditions driven by muscle aging, like sarcopenia and frailty.”

BioAge is committed to advancing molecules and programs that promote healthy longevity by targeting fundamental mechanisms of aging and Fortney says that BGE-105 is a perfect example of this.

“Analysis of our human aging cohorts showed that apelin signaling is a key aging pathway that is strongly linked to future mobility, cognitive function, and all-cause mortality,” explains Fortney. “We anticipate applications for this molecule for a broad range of chronic conditions.”

There are indications that the apelin pathway may play a role in other longevity and/or cognitive functions and Fortney told us that BioAge’s human data platform showed that apelin may be playing roles beyond muscle.

“Higher apelin activity is correlated with both healthy longevity and cognitive function, in addition to more directly muscle-related endpoints like mobility,” Dr Forney explains. “We’re at a much earlier stage of studying the impact of apelin on the aging brain and cognition, but we’re excited about this research direction. The molecular mechanisms that drive aging have the potential to address multiple different diseases and morbidities — and our analyses of human longevity data tell us that apelin signaling has exactly the features we’d expect for a key aging pathway.”

BioAge’s Phase 2 trial is anticipated to begin in 2023, and the company is also set to continue to develop the drug for chronic conditions related to muscle aging.

BioAge is hosting a virtual event in which company leaders and key opinion leaders discuss the results of the Phase 1b trial, the design of the upcoming Phase 2 study and
the significant unmet need for therapies for ICU diaphragmatic atrophy. This is scheduled for 4th January 2023, and interested parties can register for the event here.