A 'Reverse Aging' Guru's Trail of Failed Businesses --- Harvard geneticist David Sinclair aims to develop treatments for aging, but his companies have struggled to deliver

"Harvard geneticist David Sinclair's seductive notion that aging is a treatable disease has helped companies he founded to raise more than $1 billion. The investors have almost nothing to show for it.

Four companies trying to develop longevity drugs have gone bankrupt or largely halted operations. Another four either haven't yet tested their drugs or gene therapies in humans or have run only small-scale trials that make it difficult to know whether a drug will work.

Yet none of that has dented Sinclair's status as the longevity business's brightest star and chief salesman. Not only has he turned ideas from his own Harvard lab into commercial ventures, other entrepreneurs, attracted by his clout with both consumers and other scientists, have brought him in as a co-founder of their companies.

Sinclair also has co-founded companies that sell directly to consumers products such as antiaging dog chews, supplements and tests that purport to show one's "biological age."

Over the years, Sinclair's business pitch has remained largely the same: Aging can be slowed or reversed, and we are about to figure out how.

"A lot of my colleagues dislike that phrase, the reversibility of aging," he told a roomful of longevity investors in September at a conference in Gstaad, Switzerland. "But I truly believe that, based on my lab's research and now others, that aging can be reversed. If I can make one medicine that would change people's lives, I'd be very happy."

Talk like that has drawn criticism from fellow scientists, who say Sinclair tends to exaggerate the findings and implications of age-related research, tarnishing a nascent field vying for credibility. The board of the Academy for Health and Lifespan Research, a group Sinclair co-founded and led, asked him to resign as president earlier this year after he was quoted as saying a dog chew sold by a company he co-founded, Animal Biosciences, reversed aging in dogs.

It isn't unusual for startups based on unproven science to go bust. Promising drugs regularly fail when moved from the lab into the real world. Compounds safe for mice prove toxic to people. Moreover, getting Food and Drug Administration approval for longevity drugs is complicated by the fact that the agency doesn't consider aging a disease.

Some institutional investors are steering clear. "I am not a huge fan of longevity," said Dr. Christiana Bardon, co-managing partner of biotech-investment company MPM BioImpact, noting that trials to assess lifespan extension are difficult to run. "I don't have any proof any of these magic bullets have an effect."

The notion that science can keep people young, though, has captivated many in Silicon Valley. In 2013, Google launched Calico Life Sciences, a company focused on the biology of aging that has $2.5 billion in funding. Cell-reprogramming company NewLimit was founded in 2021 with $150 million from investors including Coinbase founder Brian Armstrong. Altos Labs opened in 2022 to pursue cell rejuvenation, raising $3 billion from investors including Yuri Milner, an early Facebook backer.

Sinclair, who is 55 years old, said in an email that companies he co-founded that went public "paved the way" for many of today's longevity companies. "In the mid-2000s, it was not widely recognized that aging research could be a legitimate path for developing drugs to treat both rare and common disease," he said. "Science has its successes and failures, but the most important thing is you keep learning, discovering, and trying to move the discipline forward."

Sinclair's business career began in 2004 when he co-founded Sirtris Pharmaceuticals. His lab found that resveratrol, a compound found in red wine, appeared to prolong lifespan in worms, yeast and other organisms. Sirtris wanted to make a reformulated version. He was among the first to get a big pharmaceutical company to buy into the notion that a longevity drug could get to market, selling Sirtris in 2008 to GSK -- then GlaxoSmithKline -- for $720 million. His shares at the time were worth $9.3 million.

He clinked a glass of red wine with Barbara Walters that year on a special called "Live to be 150 . . . Can You Do It?" Walters asked how much wine she would have to drink to benefit from resveratrol. Sinclair said 1,000 bottles a day, but added that he could make a version of resveratrol that would be more potent.

The segment included a video of a mouse on a high dose of resveratrol running twice as far on a treadmill as an untreated mouse. Sinclair said the mice on resveratrol didn't get heart disease, cancer, or osteoporosis and lived 30% longer. "We think resveratrol can have similar benefits in people," he said.

When Walters pointed out some people might be skeptical, he responded: "I agree. But it's true. What else can we say?"

In 2010, GSK stopped testing the drug in cancer patients over safety concerns. Three years later, GSK announced it was closing Sirtris.

"I think if it was still under my care and passion, [Sirtris] would have had a champion," Sinclair told an audience at the Aspen Institute this July. He got a laugh when he said that elderly people simply need a reboot. "The good news is we can do it in mice. I don't think it will be that long in people," he said. "Technology is going so fast even I, as an optimist, underestimate the pace of change."

Although Sirtris ultimately failed, its lucrative sale to GSK energized a field once considered a research backwater, and gave Sinclair cachet and connections.

In 2011, Sinclair and colleagues from Sirtris founded OvaScience to commercialize research they believed would help older women become pregnant. It went public in 2012.

In a presentation in December 2014, Sinclair told OvaScience investors that traditional in vitro fertilization treatments often fail because the amount of "chemical energy" inside an older woman's eggs is too low. OvaScience's treatment, he said, could effectively reverse an egg's age with stem cells harvested from a woman's own ovaries, boosting its energy levels enough to promote fertilization.

Sinclair told them he saw the technique as a test case of antiaging technology, and that his role was to connect the scientist who had pioneered the treatment with financial backers. In a half-century, he said, people would look back at OvaScience's work as "the beginning of a new chapter in the way that humans can control their bodies . . . It may not be 50 years actually. It may be only 10, the way things are going."

The next day, OvaScience shares jumped 24%, to $43. The stock peaked in March 2015, at $53, which valued the company at more than $1.3 billion. Sinclair's stake of more than 700,000 shares was worth some $37 million at the time, according to the Journal's analysis of regulatory filings.

Later that month, OvaScience said its treatment hadn't improved IVF success rates in patients. Its shares tumbled 35%, to $34.73. By March of 2018, the stock was trading for less than $1.

By then, OvaScience had abandoned the fertility treatment, according to SEC filings. The company had limited revenue when it was effectively acquired by Millendo Therapeutics in a reverse merger in 2018.

Around the time OvaScience's stock was peaking in 2015, another company Sinclair co-founded, CohBar, was going public to develop treatments for obesity and fatty liver disease. The founders raised nearly $75 million overall. In a shareholder presentation that year, the company featured Sinclair's selection in 2014 as one of Time's 100 Most Influential People.

"He was sort of the ultimate scientist-entrepreneur," said Dr. Pinchas Cohen, a CohBar co-founder and the dean of the University of Southern California Leonard Davis School of Gerontology, in an interview.

CohBar's great hope, a synthetic version of a natural hormone, had been used to treat obesity and fatty liver disease in mice. After going public, CohBar conducted small studies in humans testing the safety of the drug.

In May 2018, CohBar said stockholders planned to sell more than 27 million shares. Sinclair listed more than 800,000 shares for sale.

In financial disclosures, CohBar repeatedly called into question its ability to continue as a going concern. In 2022 it suspended development on its leading drug candidates, citing safety concerns and disappointing study results.

Shareholders sued CohBar in 2023, saying they had been misled about a merger CohBar planned with oncology company Morphogenesis. The merger fell apart that year and CohBar said it would dissolve.

In 2017, Sinclair co-founded Life Biosciences, a longevity incubator set up to turn promising findings from scientists' labs into startups. Life Biosciences expanded rapidly, forming subsidiaries and growing to 90 employees. Over the years, it raised about $158 million. It licensed a gene therapy from Sinclair's Harvard lab to develop as a possible treatment for a rare eye condition that causes sudden vision loss.

Sinclair appeared that year in an NBC News segment titled, "Researchers say they are close to reversing aging," promoting his lab's work on genetic reprogramming for vision loss in mice and brain cells.

"So maybe once a year you go get a prescription from your doctor, you take it for a week, and it reverses your aging, is that your vision here?" asked the journalist, Dr. Akshay Syal.

"It's not just a vision," Sinclair responded. "It's going to happen. It's like asking the Wright brothers, 'Are we going to fly?' Of course we are. It's just a matter of when."

Life Biosciences closed subsidiaries, cut its workforce to 13, shut its lab and contracted most work on the therapy to outside researchers, Chief Executive Jerry McLaughlin said in an interview.

Life Biosciences has since shared data at conferences that it said showed the therapy restored some visual function in monkeys. Executives met with the FDA last December to discuss what evidence they would need to start a trial in people. McLaughlin said Life Biosciences hopes to start a trial by 2026.

Life Biosciences has changed from an incubator to a biotech focused on reprogramming cells, McLaughlin said. Sinclair remains on the company's board but doesn't direct its science.

At the Aspen Institute in July, a woman in the audience asked Sinclair when a Life Biosciences drug might be available for glaucoma.

FDA approval could take four to five years, Sinclair responded. "By the end of next year," he said, "I will likely be able to tell you if it works."

Metro International Biotech, which Sinclair helped found in 2016, is trying to develop a formulation of nicotinamide mononucleotide, or NMN, as an FDA-approved drug to treat age-related conditions such as Alzheimer's disease. NMN has already been marketed to consumers as a longevity-promoting supplement, and Sinclair frequently speaks about how his elderly father takes it daily as part of his longevity regimen.

In recent years, Sinclair has started consumer-oriented businesses.

In 2022, he and celebrity chef Serena Poon, who he describes as both his personal partner and business partner, started Fully Aligned, which calls itself a consumer wellness company.

He co-founded Tally Health in 2022 with Whitney Casey, a partner at a private-equity firm. Casey got interested in the Sinclair lab's efforts to develop a cheek-swab test to tell people their biological age, a measure of how fast their body is aging physically rather than chronologically. Tally started selling $229 test kits.

Biological-age tests haven't been proven to effectively measure and monitor health, many scientists say. Casey said Sinclair left Tally's board due to a conflict of interest when the company began selling its products. Sinclair said he remains "enthusiastic" about biological age tests, "with continued improvements in their accuracy."

Sinclair said he believes that his companies will someday produce life-changing medicines. "Developing medicines that safely and effectively target aging," he said, "is a difficult endeavor that has turned out to take longer than I expected."" [1]

1. A 'Reverse Aging' Guru's Trail of Failed Businesses --- Harvard geneticist David Sinclair aims to develop treatments for aging, but his companies have struggled to deliver. Marcus, Amy Dockser; Janin, Alex; Shifflett, Shane.  Wall Street Journal, Eastern edition; New York, N.Y.. 07 Dec 2024: A.1.