A Longhorn Is Developing Therapeutics to Extend Lifespans—Starting With Man’s Best Friend

By David Silverberg in Features, July | August 2023 on June 30, 2023 at 7:00 am | 2 Comments

When Celine Halioua was just 18 years old, she spent the summer before her first year  
at UT as an intern at a neuro-oncology clinic. There, she met several patients with terminal brain cancer. It was a formative, perspective-altering experience for the budding scientist.

“At that age, I thought that if something goes wrong, a doctor can save you,” Halioua, BSA ’17, says. “It was scarring for me to realize there are many diseases, predominantly age-related, that if you get them, it doesn’t  matter how much effort or time or money you put into it; there’s not much anybody can do for you.”

Halioua carried that realization into her sophomore year, when a door of opportunity opened. While living at the all-female dorm Kinsolving Hall, she picked up a newsletter advertising summer jobs. At the very bottom, she spotted an ad to work as an intern at the nonprofit SENS Research Foundation to conduct stem cell-based research on Parkinson’s and Alzheimer’s therapeutics. “I applied, got the internship, and it ended up changing my life,” Halioua says.  

SENS offered her a fellowship to work at Sanford Burnham Prebys in Dr. Evan Snyder’s lab to study Parkinson’s disease. But she soon got frustrated when she better understood the challenges in developing a therapy to replace neurons, a key nuance in trying to manage Parkinson’s.   

“I became curious about why we aren’t working on preventing patients from developing this disease in the first place. Why aren’t we working on delaying the onset of Parkinson’s?” she says.  

At that moment, anti-aging therapeutics became her calling. And a few years later, she found the lens through which she would focus her work.  

In 2019, Halioua was sitting around a campfire with friends in the South Bay near Los Angeles, drinking and chatting. She half-joked about her idea to make dogs live longer. But as she spoke, she realized she wasn’t exactly joking.  

“Big dogs metabolically age faster; they lose resilience faster,” she says. “A 4-year-old Great Dane will often have a grey muzzle when a chihuahua doesn’t look old until they are 12 or older.” The idea? “Turn off or dampen down that growth pathway to slow that rate of aging.”  

From there, it was like a game of corporate telephone. An angel investor on the trip told his friend about Halioua’s idea, and then that friend brought up the notion to venture capitalist Greg Rosen, who was intrigued about pet genomics. He asked this friend to arrange a coffee meetup with Halioua, and after that, the idea had legs.  

Rosen coached her for three months on fleshing out the idea. He asked her if she was willing to leave her job at the Longevity Fund, start a company, and take a first round of investment he would lead.   

“He essentially convinced me to lead the company,” Halioua says, adding that she was excited to work in a field she felt was ripe for innovation. Plus, she geeks out about this kind of science.  

“At school I fell in love with molecular pathways and understanding how cell biology works, which is really key to aging,” she says.  

Months later, after a deluge of admin work and hiring sprees, her company, Loyal, was born, brimming with $5.1 million in funding.   

Based in San Francisco, Loyal aims to develop therapeutics that extend both the longevity and vitality of dogs, which Halioua says is the first step in developing a similar drug for humans.  But why start with dogs? Think of it this way: As the old adage goes, one human year roughly equals seven dog years. This means researchers can study the aging process in dogs much faster than in humans. With shorter lifespans and similar age-related illnesses and diseases as humans, dogs are the perfect candidate.   

Halioua explains, “If you hit a mechanism or find a drug or find a pathway that works in dogs, then it might also be relevant in people.”  

One drug under trial is focused on big dogs. Ask Halioua to explain the science behind the drug and she delves deep into the biology and breeding history of canines, speaking in the self-assured and sometimes dizzying language of someone who has spent years in labs.   

“The thesis of Loyal’s drug that we call LOY-1 is that the big dog’s short lifespan is a genetically associated disease,” she says. Different breeds have different struggles: Dogs with flat faces struggle with breathing. German shepherds often have hip dysplasia. Golden retrievers have a couple forms of cancer that are very high in those breeds.   

“We compensate for the genes that we accidentally selected for dogs to make them big, but also seem to cause them to age faster,” explains Halioua, “to slow the rate of aging of big dogs to potentially extend their lifespan.”   

The genetic pathways that cause a dog to grow very fast in puberty should shut off after the dog is fully grown, but they don’t shut off in larger dogs. In this trial, the idea is to basically turn off—or dampen down—that growth pathway to slow that rate of aging.  

LOY-1 would be a dissolvable implant, similar to how vets put a microchip under a pet’s skin, which would release the drug over three to six months.   

The company is also focusing on tackling other conditions a dog may develop, such as dementia and kidney failure, through the development of a pill that delays the onset of age-related diseases.  

Both drugs have yet to win FDA approval, and they are currently being tested on various groups of dogs, such as beagles. These trained dogs know how to do a certain battery of cognitive tests, she explains, and her team is studying if they perform better, neutral, or worse on various measures of cognitive function after receiving Loyal’s drugs.  

“My goal with Loyal is to build an aging pharmaceutical company, and I think aging drugs will be a class as large or larger than oncology and neurodegenerative disorders,” she says. “I don’t think any one company’s going to own the space, but I do want to be part of the team and the people that bring this space into normalcy.”  

Both drugs are estimated to be available by 2026, according to Halioua.  

But how does this research sync with the potential to extend human lifespans? Halioua explains that dogs are one of the best models of human aging since they also develop the same age-related diseases we do at approximately the same time in their life.   

“A drug that works on extending the healthy lifespan of dogs is not one-to-one to working to people,” she cautions.  “But it is much more reasonable to believe that if you hit a mechanism or find a drug or find a pathway that works in dogs, that it might also be relevant in people. It also is beneficial because it’s a much faster feedback loop. If I gave you a potential aging drug today, I’d have to wait decades to see if it does anything. In dogs, that’s just not the case. We wait a few years.”  

Long before she had dreams of developing breakthrough anti-aging drugs, Halioua was living in Austin with her parents and their 15 cats and three dogs. As a kid, her love of animals was only matched by her passion for science.   

While at UT studying neuroscience, she immersed herself in two freshman research initiative labs: an MRI lab, which studied traumatic brain injuries in soccer players, and a nanocluster research group, which worked on creating material that is less than 100 nanometers in diameter.  

“The best thing UT ever did for me was allow me to be in multiple labs at once,” Halioua remembers. “The coursework was interesting, and it gave me a good foundation in biology and chemistry. That’s necessary when you’re doing anything in the science spaces.”  

Dr. Regina Mangieri, Research Assistant Professor of Pharmacology & Toxicology at UT, recalls mentoring the undergraduate and noticing her motivation and how she asked smart questions.  

“It doesn’t surprise me Celine started her own company. She always had this positive, let’s-just-try-it attitude,” Mangieri says.  

But what was exciting to learn—the numerous studies introducing potential drugs to slow aging—also gave her pause. As she wrote in a Medium post in 2018: “The field of aging is uniquely prone to pseudoscience, driven by the internalized fear most have of becoming old, debilitated, and dying.”  

Halioua studied at Oxford before joining the Longevity Fund, a venture-capital fund focusing on aging-related startups in Silicon Valley, which gave her a chance to pore over pitch decks and speeches dedicated to anti-aging. The gears began whirring faster in her head, and by the time of that fated campfire, her entrepreneurial dreams began to take shape.   

Investors were struck by her dedication to this burgeoning space. “As a fund, we tend to invest under the principles of being bold, early, and impactful,” says Shernaz Daver, operating partner and CMO of Khosla Ventures. “Celine is a passionate and a very determined founder, and Loyal is doing truly hard work that has never been done before.”  

That work ethic has taken Halioua out of the lab and into the boardroom. “My job as CEO is to ensure everybody’s aligned and running toward the same goals,” she says. “Fundraising is a big part of my job, too. Making drugs is expensive, so I have to make sure we have the capital to fund the research we need to do before we start bringing revenue into the company.”  

What she also finds fulfilling about her work at Loyal, now at 60 employees, is inspiring young women to take a chance on their startup dreams.  

“I want to show people how a woman can build a deeply technical company …,” she says with a smile. “You can work on moonshots and not look like Elon Musk.”  

CREDITS: Karsten Winegeart