Autophagy-enhancing drug candidate enters Phase 1 trial as longevity focused biotech eyes Alzheimer’s as a potential first indication.
Longevity biotech Retro Biosciences has achieved its goal of becoming a clinical-stage company in 2025, after dosing the first participant in a clinical trial of its autophagy-focused drug candidate. The San Francisco–based company enters the clinic following reports earlier this year that it was preparing to raise as much as $1 billion to support its next phase of growth, having already raised a $180 million seed round funded exclusively by OpenAI boss Sam Altman.
Retro’s clinical drug candidate, RTR242, is a small-molecule therapy designed to restore lysosomal function, a core component of autophagy – our cells’ waste-handling and recycling system. In healthy, younger cells, lysosomes maintain an acidic environment that allows the autophagy process to break down damaged proteins and cellular debris. As people age, and particularly in neurodegenerative diseases such as Alzheimer’s, lysosomes lose acidity and efficiency. The result is a buildup of toxic protein aggregates that place chronic stress on neurons and contribute to their dysfunction and eventual loss. Retro’s approach aims to repair this decline at its source, reactivating the cell’s own cleanup machinery rather than targeting the problem downstream.
By restoring lysosomal function, RTR242 is intended to help neurons clear harmful proteins more effectively and return cellular behavior toward a more youthful state. In Alzheimer’s, Retro suggests its approach could address the underlying cellular failures that accumulate over time rather than attempting to compensate for damage after it has already occurred – potentially enabling intervention before significant cognitive decline begins.
The Phase 1 study is a randomized, double-blind, placebo-controlled trial in healthy volunteers, conducted at a specialized early-phase clinical unit in Adelaide, Australia. In addition to standard safety and tolerability measures, the study includes exploratory biomarkers tied to autophagy and lysosomal biology, giving Retro its first opportunity to observe whether its mechanistic hypotheses translate into measurable biological signals in humans. Failures in cellular clearance are a common feature across many degenerative conditions, so if the biology proves tractable in humans, the hope is that the approach could have applications beyond neurodegeneration, informing approaches to other disorders where accumulated cellular damage plays a central role.
In addition to autophagy, Retro is working on multiple approaches focused on aging biology to extend human healthspan, with additional programs in cellular reprogramming and microglia therapeutics. In cellular reprogramming, the company is building on the Nobel Prize–winning discovery that mature cells can be reverted toward a more youthful, pluripotent state using a set of transcription factors known as the Yamanaka factors. In a collaboration with OpenAI, Retro applied a specialized AI model trained for protein engineering to redesign key components of its reprogramming cocktail. The resulting engineered transcription factors showed markedly higher efficiency in lab experiments, accelerating the appearance of stem cell markers and improving indicators of DNA damage repair, a central hallmark of aging.
Retro is also exploring cell therapies, including one aimed at rejuvenating the brain’s immune cells, microglia, which become chronically inflammatory with age. By replacing dysfunctional microglia with younger counterparts, Retro hopes to address another fundamental driver of neurodegeneration that operates alongside protein accumulation and neuronal stress.
