Cell Reset Therapeutics to Extend Healthspan and Lifespan (Janine Sengstack, Junevity)

Translating Aging

Dr. Janine Sengstack is the Chief Scientific Officer and co-founder of Junevity, a company created in 2023 with the mission of extending health span and lifespan through what they term "Cell Reset therapeutics." The company recently secured $10 million in seed funding.

In this episode, Chris and Janine explore the innovative platform Janine developed during her PhD work in Hao Li's lab at UCSF, which now forms the foundation of Junevity's therapeutic approach. They discuss how the company uses computational and experimental methods to identify transcription factors that can "reset" cells from a diseased, aged state back to a healthy state while maintaining cell identity. Janine explains how Junevity is developing siRNA therapeutics targeting these transcription factors to treat age-related diseases, with a focus on metabolic conditions and other disorders that impact longevity.

The Finer Details:

• The development of the Reset platform during Janine's PhD work and its evolution into Junevity's therapeutic approach
• How transcription factors act as "managers" in cells, regulating many other genes
• Using AI and machine learning to identify the right transcription factors to target based on disease and tissue-specific data
• The validation process for siRNA therapeutic candidates in cell and animal models
• Junevity's focus on diseases with large-scale transcriptional dysregulation, including type 2 diabetes, obesity, muscle wasting diseases, and osteoarthritis
• The advantages of siRNA as a therapeutic modality for targeting traditionally "undruggable" transcription factors
• Junevity's business strategy and timeline, with clinical trials potentially beginning in 2026

Quotes:

"We tackled this high risk, high reward PhD project: we were inspired by the Yamanaka factors to say, 'Okay, let's find brand new transcription factors that we can target to take cells from a diseased, old state and bring them back to a healthy state while keeping them the same cell type, never turning them into a stem cell.'"

"Transcription factors: I like to think of them as managers in the cell."

"We think the advent of modern AI and machine learning tools to better analyze what they regulate, plus siRNA as a really well-proven therapeutic modality, really unlocks the ability to target transcription factors and really make powerful therapeutics with them."

"We're thinking about using transcriptional regulation as a way to come up with novel therapeutics to treat diseases that have a big impact on people's health span and lifespan."

"We want to advance our programs towards development candidates, which basically means the drug entity, and move them forward towards clinical development as fast as possible."

"I would love if we had multiple siRNA drugs on the market, ideally, or in late stages of development for a wide range of longevity-related diseases... We think that there's really huge potential here for making a big impact on a lot of different really complicated diseases."

Links

https://www.junevity.com