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

Dr. Andrew Brack, Program Manager at the Advanced Research Projects Agency for Health (ARPA-H), discusses PROSPR (Proactive Solutions for Prolonging Resilience), an ambitious new program aimed at extending human healthspan. In this wide-ranging conversation, Chris and Andrew explore how PROSPR plans to accelerate the development of therapies that target aging itself by building the regulatory and scientific infrastructure needed to measure and improve health during aging. They discuss PROSPR's innovative approaches to in-home data collection, biomarker development, and clinical trial design that could compress decades-long studies into just three years.

The Finer Details:

• The mission and structure of ARPA-H as a catalyst for healthcare innovation
• How PROSPR aims to build "train tracks" for the longevity therapeutics industry
• The program's novel approach to measuring health through intrinsic capacity
• Strategies for compressing clinical trials from decades to years
• The economic impact of extending healthspan by just one year
• Plans for first- and second-generation therapeutics targeting aging
• The role of in-home health monitoring in future clinical trials

Quote:

"We have this moral imperative to close the gap between the length that we are living and the number of years that we're living in good health."

Links:

PROSPR website

Proposers' Day registration

Markus Gstöttner is the CEO of Clock.bio, a company devoted to extending and improving the quality of life by reversing the harmful effects of time in our cells. In this episode, Gstöttner shares how his company is working to extend healthspan by understanding and harnessing the natural rejuvenation capabilities of stem cells. The conversation explores Clock.bio's groundbreaking approach to identifying the genes and pathways involved in cellular rejuvenation, and their vision for translating these discoveries into therapies.

The Finer Details:

• How induced pluripotent stem cells (iPSCs) naturally resist and reverse aging
• Clock.bio's novel platform for forcing stem cells to age and studying their spontaneous rejuvenation
• The company's comprehensive genetic screen identifying over 150 rejuvenation-related genes, the Atlas of Rejuvenation Factors
• Strategies for validating these discoveries and developing therapeutic applications
• The path from discovery to clinical trials for extending human healthspan