BioAge CEO reflects on clinical trial progress and using AI to build a longevity biotech development pipeline spanning muscle, immune and brain aging.
Powered by data produced by its AI-driven discovery platform, clinical-stage biotech BioAge Labs is rapidly developing a pipeline of therapies to extend healthy lifespan by targeting the molecular causes of aging. Having raised more than $120 million in funding, and with multiple clinical trials already under its belt, the company is focused on building a broad pipeline of potential longevity therapies in three main areas: muscle, immune, and brain aging.
Longevity.Technology: There are few companies in the longevity biotech field that appear to be executing on their vision as quickly and consistently as BioAge. When the company wowed the sector with a $90 million funding round in 2020, talk of multiple imminent clinical trials may have sounded optimistic to some, but BioAge has delivered on its promise time and again. Beyond the trials already underway, the company’s much-vaunted AI discovery platform also appears to be churning out the data, this year spawning a new programme exploring the potential of NLRP3 inhibitors in brain aging. To learn more, we caught up with BioAge co-founder and CEO Kristen Fortney.
Looking back at 2022, Fortney says it has been “immensely gratifying” to see so many new companies and investors coming into the longevity field.
“Given that aging is the primary risk factor for most chronic diseases, the enthusiasm about these companies is amply justified,” she says. “And though this might feel like rapid growth – and it is! – remember that the total capitalization of the longevity biotech sector is only about one percent of the market cap of the public companies in the other sectors of pharma. We’ve seen an upwelling of interest and investment, but we have a lot further to go before the field has the resources it deserves. This is still just the beginning.”
Reflecting on what the past 12 months have meant for BioAge, Fortney hails 2022 as a “great year.” The company’s mission of developing a pipeline of treatments that extend healthy lifespan by targeting the molecular causes of aging has, she says, experienced “forward momentum on all fronts.”
“We announced a new class of NLRP3 inhibitors that we developed in-house, expanded our platform into the key area of brain aging, established a new biobank that will dramatically accelerate our ability to discover and target new aging mechanisms, and – most recently and most exciting – announced positive topline data from our Phase 1b trial of our compound BGE-105, which combats muscle atrophy.”
Muscle aging drug shows promise
BGE-105 is a “first-in-class apelin receptor agonist” and part of BioAge’s most advanced clinical programme in muscle aging. Fortney says that the data from the Phase 1b trial were “quite striking.”
“In healthy volunteers aged 65 and older on 10-day strict bed rest, BGE-105 significantly prevented muscle atrophy vs. placebo, preserving muscle mass, dimensions, and protein synthesis,” she says. “BGE-105 is another great example of our platform at work. In our aging cohorts, apelin pathway activity is correlated with longevity, mobility, and even cognitive function, implying that loss of apelin activity is a key aging mechanism that drives multiple diseases and morbidities – exactly the kind of target that most interests us.”
The trial findings, explains Fortney, are exciting for several reasons.
“First and foremost, the data support advancement of BGE-105 to a Phase 2 trial for prevention of ICU diaphragmatic atrophy and critical illness myopathy,” she says. “In immobilized and mechanically ventilated ICU patients, acute myopathies lengthen recovery times, increase the risk of complications, and drive high morbidity and mortality. Although these conditions affect millions of people every year, no therapy is currently available. A therapy that could alleviate critical illness myopathies could have a huge positive impact on clinical outcomes, and we are very excited about the potential of BGE-105 to meet this high unmet medical need.”
BioAge plans to initiate the Phase 2 trial of BGE-105 later this year.
“Over the course of the 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 for chronic indications with extremely high prevalence, such as sarcopenia and frailty,” says Fortney. “More broadly, our positive Phase 1b trial outcome shows that we can go from human longevity data through target discovery to successful trial of a clinically relevant drug, validating BioAge’s discovery platform and our approach to identifying targets.”
Muscle aging: an unmet need
The wider challenges associated with age-related muscle atrophy are, says Fortney, an enormous area of unmet medical need.
“In addition to the acute myopathies we’re focusing on in our Phase 2 trial of BGE-105, loss of muscle with age leads to sarcopenia and frailty, chronic conditions that drive multiple morbidities, shortening lifespan and decreasing quality of life in a large proportion of the aging population,” she explains. “These conditions are especially pernicious because they create negative feedback cycles: loss of muscle increases the risk of injurious falls, which force patients to be immobilized during recovery, leading to further atrophy.”
Because no therapeutics are currently approved for muscle aging indications, reduced mobility is often seen as an “inevitable” consequence of aging.
“By developing therapies for diseases driven by muscle aging, we’re addressing another one of the greatest fears about growing old – loss of autonomy – and ultimately working toward a world in which we can keep our loved ones out of nursing homes, and older people can continue to live fully independent lives,” says Fortney.
AI points to NLRP3 inhibitors
BioAge’s new NLRP3 inhibitor programme is a good example of the company’s AI discovery platform in action, and demonstrates the company’s ability to go rapidly from a key aging target to novel, promising lead compounds.
“The story starts with our human aging cohorts, which include biological samples collected over decades of lifespan coupled with detailed health records for each sample donor,” says Fortney. “Omics data from these samples allow us to ask what molecular differences predict which people will live the longest, healthiest lives. The health data also include assessments of brain function, so we can also probe the molecular features correlated with risk of future cognitive decline.”
Fortney explains that, using these cohorts, BioAge’s AI-driven analyses showed that NLRP3 inflammasome activity rises with age and is associated with all-cause mortality and cognitive decline. This suggested that inhibition of NLRP3 has the potential to prevent multiple age-related disorders driven by pathologic inflammation.
“After identifying this important target, we performed DNA-encoded library (DEL) screening to create a novel class of molecules that potently inhibit NLRP3,” says Fortney. “Some of these inhibitors can cross the blood–brain barrier and are therefore of particular interest from the standpoint of neurodegenerative disease.”
“This is the first time that we chose to build our own compounds, and the success of the discovery effort demonstrates that BioAge can not only select clinically relevant targets but also create great molecules de novo. This is a model we’re going to repeat again and again for compelling targets identified by the platform in the future.”
Expanding brain aging pipeline
BioAge is now continuing to develop and evaluate the NLRP3 inhibitors and explore their relevance for diseases of brain aging. Fortney says that the company aim to file an investigational new drug (IND) application in 2023.
This expansion into brain aging is a key part of BioAge’s development strategy, and the company recently appointed Dr Peng Leong as its Head of Brain Aging to lead the expansion of its platform in this new direction.
“A broad range of different pathways are involved in brain aging, and the human aging data at the foundation of our discovery platform give us unique insight into which of these pathways are the most critical drivers – and thus which are the most promising targets for therapeutic intervention,” says Fortney. “Peng helped to build the partnerships that enabled rapid growth of the Company’s clinical programs based on our discovery platform, and he continues to be an essential member of our leadership team. Starting from this promising foundation and leveraging other insights from the platform, Peng is already making great strides in helping BioAge discover new therapeutics in this critical area.”
Gearing up for 2023
Looking to the year ahead, BioAge’s top priority is, of course, advancing its clinical programs, but improving the capabilities of its AI-powered drug discovery platform is also a key objective.
“The platform itself is dynamic and constantly improving its ability to identify novel targets for diseases of aging, and an important step this year was an expansion of the underlying data that feeds our AI-driven analyses,” says Fortney. “We entered into a partnership with the Norwegian company Age Labs giving us exclusive access to samples and health records from the Nord-Trøndelag Health Study (HUNT) biobank, collected from more than 100,000 subjects over more than 25 years of lifespan. We’ll apply our machine learning methods to omics data from these samples to reveal the key molecular mechanisms of healthy human longevity.”
And BioAge is also keen to support the longevity field more broadly.
“Aging research has long gone understudied and underfunded, so helping to shape the evolving field is incredibly exciting for our team – because our work at BioAge, and the efforts of the field as a whole, have the potential to impact everyone’s lives by supporting better health as we grow older,” says Fortney.