How Can You Target Pathways Involved in Aging?

Dr. Hanadie Yousef is a scientist, aging biology expert and the co-founder and CEO of Juvena Therapeutics, a Palo Alto-based biopharma startup developing protein-based therapeutics to promote tissue regeneration and increase healthspan to prevent, reverse, and cure degenerative diseases. 

Dr. Yousef joins host Dr. Chris Patil to discuss Juvena’s premise, their use of a machine learning platform to identify proteins that have therapeutic potential, and what most excites her about turning signaling proteins into therapeutics. She answers questions about handling potential challenges within Juvena’s approach, their strategy for bringing drugs to market, and the first aging indication that they are targeting - muscular rejuvenation. Dr. Yousef outlines Juvena’s plans for a clinical study in patients with Myotonic Dystrophy Type 1 by 2023, and shares what’s coming down the pipeline next for her team. You’ll also hear about Dr. Yousef’s transition from academic science to becoming an entrepreneur, her involvement with the On Deck initiative, which seeks to increase the number of scientists, researchers, and inventors in the healthspan and longevity field, and why it’s so worthwhile to invest in anti-aging science.

The interview concludes with Dr. Yousef’s advice for potential new founders in the biotech industry. She also shares the areas of longevity science that she is most fascinated by, and offers her thoughts on how the field of aging pharma will evolve over the next five to ten years.

Episode Highlights:

• Tissues deteriorate as we get older and our ability to heal slows down - this leads to a wide variety of age-related diseases
• Juvena Therapeutics sets out to find regenerative cures for those diseases
• During the aging process, critical regenerative protein signaling pathways that are important for instructing cells and tissues within our bodies start to change
• They start becoming over-expressed or under-expressed
• There is a change and loss of healthy crosstalk between pathways that can instruct cells
• This leads to a loss of tissue homeostasis
• By understanding what is changing within us, we can use that information to target protein signaling pathways that are important for stem cell function, immune cell function, etc. in order to rejuvenate tissues and reverse the aging process
• Juvena uses a machine learning platform by combining several data modalities
• Their premise is to develop protein-based therapies that can target critical regenerative signaling pathways in our bodies to promote better regeneration
• They do this by mining secretome of the most po-regenerative source of cells, which are human embryonic, or pluripotent, stem cells
• Aging models that they use are cells derived from people who are themselves aged or who have an age-related disease
• There are challenges with every therapeutic intervention targeting the biology of aging 
• Juvena’s strategy for bringing drugs to market and the first aging indication they are targeting
• They are looking to promote tissue-specific rejuvenation, for example, better muscle differentiation, reduced atrophy and improved strength and function
• They are hoping to have FDA approval as an investigative new drug within the next year and a half - this would lead to a Phase One/Two clinical study for patients with Myotonic Dystrophy Type 1 by 2023
• Dr. Yousef’s academic background and transitioning to starting her own company
• She has a passion for both drug discovery and taking those inventions to build companies
• The inspiration and motivation behind starting Juvena Therapeutics with co-founder Dr. Jeremy O'Connell, as well as the process of pitching and acquiring funding
• Dr. Yousef was torn between an academic career and entrepreneurship, and she ultimately decided to embrace her role as CEO and focus on building the company
• How investors react to Juvena Therapeutics’ aging focus and how Dr. Yousef puts their minds at ease with regards to the expense of biotech and therapeutic investment
• It’s worth the risk - with a looming healthcare crisis of an aging population around the corner, the company that succeeds in anti-aging science could be one of the most lucrative and successful companies in the world
• Dr. Yousef’s involvement in the On Deck initiative - a fellowship program that seeks to increase the number of scientists, researchers, and inventors in the healthspan and longevity field
• Advice she would give new entrepreneurs in this field
• She is fascinated by the study of human centenarians, reproductive aging, and plant aging
• Her predictions for the field of aging pharma in the next 5-10 years

Quotes:

“As we all know, tissues deteriorate as we get older, and our ability to heal slows down, which leads to a wide range of age-related diseases. So Juvena Therapeutics sets out to find regenerative cures for these disorders.”

“Through years of dedicated research, we discovered that the cures had been within us all along.”

“By understanding what is changing within us, we can actually use that understanding to target those protein signaling pathways that are so important in regulating stem cell function, immune cell function, tissue regeneration and repair, in order to rejuvenate tissues, and to actually reverse the aging process and to bring our bodies back internally to a more healthy state.”

“Ultimately, our premise at Juvena is to develop protein-based therapies that can target these critical regenerative signaling pathways in our bodies to promote better regeneration.”

“What we're doing with our machine learning enhanced platform is really building a map of regenerative protein biology with a compounding database that's enabled by an array of in-house machinery and computational tools that we establish using these data modalities, to really identify the proteins that have therapeutic potential.”

“What excites us about actually turning signaling proteins into therapeutics is their ability to really interact in more of a systems biology level with multiple pathways.”

“Of course, ultimately, the goal is to calibrate homeostatic levels of signaling to more youthful levels, and not try to over induce any one particular pathway. And so by really recalibrating, and being careful about dosing, we'll be able to avoid things like oncogenic transformation.”

“We are, right now, really interested in bringing our muscle regeneration protein therapeutic to market for a rare neuromuscular, muscle wasting disease, known as Myotonic Dystrophy Type 1.”

“Our hope is that by 2023, we will be conducting what would be a combined Phase One/Two clinical study for patients with Myotonic Dystrophy Type 1 to test if our regenerative therapeutic can, in fact, do what it's doing in all the models and all the preclinical data to date.”

“What's really coming is our ultimate goal of enhancing and promoting health span, and reversing multiple age-related and chronic diseases by developing a pipeline of protein therapies that act by rejuvenating your own body endogenous stem and precursor cell function to enhance regeneration and improve and rejuvenate your life.”

“I am a neurobiologist, stem cell biologist and aging biologist by training.”

“What came first for me was really a passion in general and biomedical research, and in the startup environment and in building companies.”

“I really fell in love with the concept that actually understanding the mechanisms driving the aging process, and specifically, the changes in signaling that occur that lead to loss of stem cell function with age, we can actually use that understanding to reverse the process, to rejuvenate stem cell function to revitalize the body, and to then really reverse aging. And so that got me so excited. And I just fell in love with that and knew that that is what I want to dedicate the rest of my life to doing.”

“It was this battle for me of, I love my research, I can really envision myself leading an academic lab and a faculty position to move this forward, really focus on brain aging. But then there was this also entrepreneurial opportunity to start my company and to instead really focus more on translational work, and really building the platform that enables a pipeline of protein therapeutics.”

“The other things investors fear is just the expense associated with some of these indications.”

“In the next decade, the largest demographic of people will be those over the age of 60. I think it's really in investors that just realize, it's worth the risk. Because the company that succeeds will be potentially one of the most lucrative, successful, and sought-after companies in the world.”

“Some advice I wish I had going into this is really looking at what the target product profile of a drug you want to develop is, and as early as possible, creating a plan to really get to that preclinical stage in that translational stage where you need significantly more investment.” 

“I think in five to ten years, we'll get increasing acceptance of aging as a risk factor to diseases and more of an acceptance of therapeutics that can target the aging process.”

Links:

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Juvena Therapeutics website