Discovering Healthspan Interventions through Phenotype-Based Drug Screening (Mitchell Lee, Ora Biomedical)

Translating Aging

Mitchell Lee is the CEO and co-founder of Ora Biomedical, a Seattle-based biotech company using large-scale phenotypic drug screening in C. elegans to discover small molecule therapeutics that extend lifespan and healthspan.

In this episode, Chris and Mitch discuss Ora's approach to drug discovery, which focuses on function and phenotype rather than specific targets or mechanisms. Using their proprietary "WormBot" platform, Ora screens thousands of compounds in parallel to identify molecules that impact lifespan, healthspan, and age-related disease phenotypes, allowing them to discover new longevity interventions in an unbiased, hypothesis-agnostic way.

Key topics:

• How Ora Biomedical was founded out of a conversation between Dr. Lee and his mentor Dr. Matt Kaeberlein about spinning out a company based on the WormBot technology
• Why C. elegans is a useful model organism for discovering fundamental mechanisms of aging that can translate to mammals
• How the WormBot platform uses imaging and machine learning to measure worm lifespan, healthspan, behaviors, and response to drugs at a large scale
• Ora's goal of screening 1 million compounds within 3 years to find the most promising longevity interventions
• Strategies for translating hits from the worm screen into rare disease therapies and direct-to-consumer natural products
• The promise of longevity interventions discovered through unbiased phenotypic screening to prevent age-related diseases and transform human health

Quotes:

Quotes have been lightly edited for clarity.

“What really sets us apart is that we do phenotypic screening, in live animals."

"If you are finding interventions that target those fundamental drivers of aging, you expect them to have multiple different impacts on age-associated diseases. But as we test more longevity interventions, we see that they also have all kinds of different impacts on non–age-associated disease models.

“It’s really just taking the geroscience hypothesis seriously: If an intervention impacts aging, it’s likely to have impacts across many different disease stages, even ones that we wouldn’t necessarily think about as being related.”

“We've seen examples of how this plays out with things like rapamycin. So it's really incredible the types of therapeutic benefits that can be had through these kinds of interventions.”

"There's going to be a never before seen boom in enthusiasm, interest, engagement, and demand for longevity therapeutics. And what we're doing today is putting ourselves in the position where we're going to be able to meet that challenge in the next three to five years."

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