Juvenity

Junevity is a preclinical-stage longevity biotechnology company developing what it calls “cell reset:” the use of long-lasting silencing RNA (siRNA) targeting transcription factors (TFs) to oppose age-related transcriptional dysregulation, which the company posits drives diseases of aging. Its initial target indications are in Type 2 diabetes, obesity, CNS, osteoarthritis, and sarcopenia.

Its scientific founder and chief scientific officer is Janine Sengstack, PhD; its co-founder and CEO is John Hoekman, PhD, the founder and CEO of Impel Pharma, which is responsible for the migraine drug Trudhesa.

The approach was inspired by Shinya Yamanaka’s Nobel Prize-winning discovery of cellular reprogramming, which enables scientists to use a defined cocktail of TFs to remove some of the epigenetic modifications of a cell that define its cellular identity (such as those of a liver or heart muscle cell).

This treatment reverts the developmental state of mature cells of a defined type into an embryonic stem cell-like state. Juan Carlos Izpisua and others subsequently demonstrated that cycles of transient treatment with these same TFs could remove some level of aberrant epigenetic modifications that accrete on aging cells, thereby restoring youthful function while retaining cellular identity.

Many longevity biotech companies have subsequently been founded to pursue partial reprogramming. The risk associated with this approach in vivo is that it may remove too much of a cell’s epigenetic landscape, compromising the cell’s identity and potentially leading to tumor formation.

Sengstack’s PhD project at UCSF sought to “reset” the dysfunctional transcriptional pattern of aging or diseased cells. They would first use large-scale human transcriptomics data and machine learning to identify gene expression pathways that become overactive in these cells, and then identify TFs unrelated to development that drive these abnormal patterns. Finally, they would use TFs unrelated to cellular identity that drive some of these aberrant profiles to normalize the cell’s transcriptional pattern (and therefore its function) without compromising cellular identity.

Juvenity has made structural modifications to its siRNA candidates to give them resistance to degradation by nucleases or other factors. Juvenity argues that because its therapies are siRNA and target TFs, they could be administered once every three or more months rather than a daily pill or a weekly or biweekly infusion, which might increase patient compliance. Additionally, Sengstack has stated that they can target their therapies to specific tissues, such as via GalNAc conjugation to target hepatocytes. In addition to its other potential advantages, 

Type II Diabetes and Obesity
In February 2025, Juvenity announced that its “first siRNA therapeutic candidate improved glucose control and insulin sensitivity in diabetic mice without causing weight gain or other side effects associated with insulin sensitizers. In obesity, Junevity’s second siRNA candidate improved adipose tissue metabolism and reduced food intake, leading to 30% weight loss versus controls. Importantly, this weight loss was driven by fat loss with retention of lean mass.”

In an interview, Sengstack described animal studies in what appear to be these models: “so many things go back to a healthy mouse state. We see decreases in things like stress response and inflammation, one of the key hallmarks of aging. We see improvements in mitochondria and fat metabolism as well. All of those pieces together add up to a healthier overall mouse, which I would argue is leading towards a resetting of the metabolism to a younger, healthier state.”

In what may or may not be the same mouse model, she said, We have some really exciting mouse data where they lose tons of fat but they don’t lose any muscle.”

In February 2025, Juvenity announced that it had raised $10 million in seed funding led by Goldcrest Capital and Godfrey Capital.