“The major modulators of aging remain to be discovered”

Buck Institute start-up Gerostate Alpha reveals work to develop small molecule drugs that simultaneously target multiple pathways of aging.

Deep in the labs of the world-renowned Buck Institute for Research on Aging, a company is growing. Founded by a team of senior Buck scientists, Gerostate Alpha is steadily working on the development of new drugs that target aging.

The three founding PhDs behind the company, Simon Melov, Gordon Lithgow and Mark Lucanic, bring more than 50 years’ combined experience in age-related science. Together, they are focused on developing new drugs to increase health span and extend lifespan by treating aging itself.

Longevity.Technology: While the company’s web site states that Gerostate Alpha is “dedicated to treating aging and age-related disease,” it doesn’t say much more than that. So when we had the opportunity to speak with co-founders Melov and Lucanic, we jumped at the chance to learn more about this mysterious company.

While many companies in Longevity are focused on addressing one or more of the hallmarks, or pillars, of aging, the founders of Gerostate Alpha always saw things a little differently.

“People take the hallmarks of aging as a launching off point, thinking that if they can forestall a particular pillar, let’s say inflammation, then they’ll get beneficial outcomes – but this is a biased approach,” says Melov. “We’ve always been interested in looking at aging mechanisms in an unbiased way, whether through genetic interventions, or pharmacological interventions, we’re not beholden to a particular mechanism, per se.”

Having talked about forming a company for years, the three founders were convinced after Y Combinator’s Sam Altman presented at the Buck in 2018 about the need to see more quality initiatives coming out of the biotech space regarding aging.

“You often hear people say they ‘target aging’ but you have to ask what does that mean… ?”

“Having been involved in the basic biology of aging and trying to understand the degenerative changes of aging from a mechanistic perspective for many years, that resonated with us,” says Melov. “And so we put together a proposal focused around some of the ideas, particularly with regard to an unbiased way to identify molecules which might retard the aging process. We pitched it to Y Combinator, they really liked us and gave us a million dollars to start the company. It was certainly the fastest million we ever made in our careers!”

And so Gerostate Alpha was born, and the team proceeded to develop its idea to screen molecules for aging, in as unbiased a way as possible. The company name, by the way, refers to someone’s “gerostate” as being the physiological outcomes of their aging process, with “alpha” indicating the best possible outcome of that process.

“You often hear people say they ‘target aging’ but you have to ask what does that mean – does it mean targeting a pillar of aging: senescence, inflammation, mitochondrial dysfunction?” asks Melov. “That’s not targeting aging – that’s targeting something other people have said is linked to aging processes. Everyone is very familiar now with using those terms, but it roots you in the idea that we understand what aging is, and we don’t think we do. We believe that these pillars of aging are just one of many, and we think that the major modulators of aging remain to be discovered.”

“The platform is geared towards identifying interventions that attenuate or halt multiple aging indications simultaneously.”

Gerostate Alpha has constructed a platform to try and identify new aging pathways, which can be manipulated to improve healthspan, function, and perhaps even increase lifespan.

“The processes of aging start early, and we’re interested in identifying those processes, and tweaking them through small molecules so that we can stop this decline or attenuate the slope and reap the benefits in terms of your individual physiologies,” says Melov. “The platform is geared towards identifying interventions that attenuate or halt multiple aging indications simultaneously. And you need the tools to do that in a preclinical model, which is tractable.”

“But we don’t want to come across as though we’re starry-eyed and using a start-up strategy to pursue intellectual questions,” he adds. “We’re targeting six major areas of unmet medical need: the CNS, muscle decline, pulmonary decline, skeletal decline, cardiovascular, and metabolic.

Many of them don’t have any medicines at all, and diseases are associated with each of those in which there’s a tremendous need for developing therapeutics. And so, although we’re targeting aging in a very genuine, robust and rigorous way, we’re also targeting it through the prism of commercialization.”

Longevity.Technology: Read the second part of our interview with Gerostate Alpha, covering the details of its discovery platform, roadmap and fundraising plans.