The Biggest Challenge for Aging

Loyal is a San Francisco-based startup that is seeking to treat the underlying causes of aging in dogs. Loyal has raised $11 million in seed funding so far, and is planning to start clinical trials of medications in 2022 and 2023. In this episode, BioAge VP-Media Chris Patil talks with Celine Halioua, CEO and founder of Loyal.

Celine beginswith by describing the striking difference in lifespan among the dog species, with smaller breeds like the Chihuahua living twice as long as larger breeds like the Great Dane. She explains how historical inbreeding to create larger dogs actually caused them to age faster, and her plan to develop a drug that compensates for this accidental genetic disorder. Celine tells us about The Healthspan Study, which tracks aging markers in dogs, as well as what inspired her to start Loyal, and how their research complements the goals of the University of Washington Dog Aging Project. Celine breaks down the role of caloric restriction in anti-aging across species, why dogs are one of the best models for human aging as a disease, her background in neuroscience and longevity, and her passion for developing drugs for healthspan and lifespan extension. Celine also offers her perspective about encountering skepticism in the biotech industry, the unique challenges faced by young women founders, and overcoming sexist assumptions following the controversial story of Elizabeth Holmes. Finally, Celine shares what’s next for Loyal and her dream to build a consumer-focused pharmaceutical company that people love.

To learn more about Loyal and their dedication to aging health for dogs, visit LoyalForDogs.com. 

Episode Highlights:

• Loyal is seeking to determine why, on average, the larger a dog breed is, the shorter their lifespan
• We do not see a 2X lifespan differential among varieties of other animals
• Loyal also looks at ways to pharmacologically improve metabolic resiliency and fitness in aged animals to give them a longer, healthier lifespan
• Historical inbreeding to create larger dogs led them to age faster once they were fully grown
• Loyal is developing a drug that plans to compensate for this accidental genetic disorder
• These drugs will enter clinical trials in 2022 to 2023
• Loyal is also running “The Healthspan Study,” which tracks aging markers in dogs (register your dog here)
• Dogs are like family to their owners, and Celine noticed how heartbroken owners were about their larger dogs aging and dying so early
• This inspired her to start Loyal
• Distinction between healthspan versus simply adding years to life
• Thesis of Dr. Matt Kaeberlein of the University of Washington’s Dog Aging Project 
• Most breeds have some sort of predisposition for some sort of disease
• LOY-001 specifically targets a cellular mechanism that is hypothesized to cause large and giant breed dogs to age faster and have shorter lifespans than their small-breed companions
• They are also developing a second drug that is explicitly for dogs of any size, who have already shown signs of aging
• Caloric restriction is one of the most fundamental agents of fighting aging - Loyal aims to replicate that effect with a drug, since most humans and dogs do not want to calorically restrict themselves
• Veterinary drugs need to be approved by the Veterinary FDA (Center for Veterinary Medicine or CVM)
• Dogs are one of the best models of human aging as a disease because they’ve largely evolved in the same environment as humans
• Because dogs have a shorter lifespan than we do, we can see whether longevity-based drugs have an impact on lifespan more rapidly than in an animal with an 80-year lifespan (like humans)
• Loyal has raised $11 million in seed funding - the largest amount for a woman solo founder
• Her goal is to show that pharmacological interventions to extend lifespan and healthspan are incredibly valuable and worthy of investment
• She has encountered skepticism in terms of both operational and societal barriers
• Going against the current helps her company stand apart in startup culture, which has been beneficial for recruiting an amazing team, 70% of which is female; but she also has to go above and beyond to prove her competence
• What’s next for Loyal and building a consumer-focused pharmaceutical company
• If they can succeed in developing a dog aging drug, it can help humans as well
• False fail risk
• The aging industry has a communal feel, rather than competitive, as we’re all pioneers in the field and individual successes are everyone’s success

Quotes:

“Fundamentally, we're developing various drug products that are targeting various concerned mechanisms by which dogs age to try to give them healthier years.”

“Specifically, our first two products are looking at one of the underlying reasons as hypothesized why smallest dogs like a Chihuahua can live 18 or more years, while Great Danes on average will live seven to eight years.”

“The larger a dog is, on average, the shorter that breed’s median lifespan, and that's abnormal. We don't see a 2x lifespan differential in humans, for example, or really any other species.”

“It's actually a consequence of historical inbreeding of dogs, that was selecting for certain phenotypes like size, that basically looks to have created almost a genetic disorder for aging in these dogs.”

“The drug that we're developing is hoping to compensate for the accidental genetic disease that we gave these dogs that causes them to become larger...and causes them to age faster after they're fully grown.”

“We are basically doing a cross-sectional, observational - that means no drug, no intervention - study, looking at large and small, old and young dogs. And the idea of this study is basically to correlate various aging biomarkers of interest for our drug programs, and also just out of interest in general, to various dog sizes, breeds and conditions.”

“There are different flavors of dog owners. But in general, people love their dogs. They see their dogs as family. They see their dogs as their furry children in some ways.” 

“Our first drug, LOY-001, is specifically indicated for large and giant breed dogs and extending their lifespan and healthspan and intervening while the dog is healthy.”

“Caloric restriction is one of the most fundamental agent interventions there is. So the question is more, How do you emulate that with a drug? Because obviously, people don't really want to calorically restrict themselves or calorically restrict their dog.”

“It's commonly accepted in the field that dogs are one of the best models, if not potentially the best model of human aging as a disease.”

“Because dogs have a shorter lifespan than we do, if longevity-based drugs are efficacious in dogs, we could see whether they have an effect on lifespan much more rapidly in an animal with a 15-year lifespan than in an animal with an 80-year lifespan.”

“Really my thing from, basically when I was 18, was how to develop better medicines for the worst diseases. And the worst diseases that I have always focused on, and been most interested in, were age-delayed diseases.”

“I felt very strongly that my goal was to explicitly develop a drug for healthspan extension and lifespan extension.”

“It's really fundamentally what I'm trying to do is prove a point to the broader population, to the medical community, to the development community, that yes, pharmacological interventions to extend lifespan and healthspan are incredibly valuable, and worthy of investment.”

“I think when I walk into a room, there’s not necessarily an assumption of competency. And I've definitely also felt a requirement of almost like perfection.”

“I'm very careful with how I word things because it's very easy, especially as a female founder, to get labeled as cocky or overconfident. So I'm much more conservative in my language than I might naturally be.”

“Basically, people don't have very positive emotions or feelings towards pharmaceutical companies, which is understandable on some variables, but also disappointing because I think we want people to be excited about spending time...and working on developing new medicines. It's, in my opinion, one of the most important things to spend your life on because health is fundamental.”

“I'm really interested in the opportunity of building a pharma company that people love.”

“Actually if you think about it, aging encompasses probably the majority of cancers, plus nerve center disorders plus sarcopenia, arthritis, all these other diseases.”

“Honestly, every company that's legitimate, that works on aging is only more helpful. It makes my life a little bit easier to prove that it's a valid thing to work on.”

“We all win if we develop better medicines, and that's kind of where it's supposed to go.”

“I feel like my only job is to help develop better medicines. So it means everything to me because I think it's the most important problem to work on.”

Links:

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Loyal website LoyalForDogs.com