Knee Injections Could Hold the Key to Fighting Aging
(Bloomberg Businessweek) -- To hear Nathanial “Ned” David tell it, the osteoarthritis drug his Unity Biotechnology began testing in human subjects last fall is about far more than just helping aging weekend warriors regrow cartilage in their damaged knees. It’s the first step toward making us all feel young again. “Aging is not a rigid, inflexible phenomenon,” he told a conference room full of Wall Street analysts and financiers in Midtown Manhattan. “Nature has created control knobs that it uses and turns to change the life span of different organisms. Finally, as scientists, we are learning how to identify some of these knobs and actually turn them as a therapeutic strategy.”
David, 51, was in New York to explain the science behind UBX0101, the drug Unity has in late Phase I clinical trials to treat the intractable arthritic condition, which affects 14 million Americans. The company is expected to release early results within the next several weeks. Analysts, scientists, and patients are watching closely.
David’s ambition is to establish a new scientific field he calls senolytic medicine. Senolytics are small molecules that can selectively induce the death of cells that have entered a state known as senescence—they no longer divide and instead trigger chronic low-level inflammation that’s harmful to surrounding cells. Senescence is associated with a wide array of diseases that occur mostly in old age, including heart disease, glaucoma, strokes, and arthritis. Purging the body of these zombie cells, David believes, could undo the ravages of time.
Unity is among a small group of companies, including the Google health-care subsidiary Calico, that are attempting to harness advances in molecular biology to increase the human health span, the length of time that a person is healthy. The idea, David says, is not just to prolong life but to allow older people to live healthier lives. “We are not purely a senolysis company. We will also be exploring alternative mechanisms that can extend human health span,” he says.
The reaction from the pinstriped crowd in New York—which included analysts from Citigroup, Goldman Sachs, and Morgan Stanley—was respectful but muted. After all, only about 12 percent of drugs that enter clinical trials are successful, according to a 2018 report by the Tufts Center for the Study of Drug Development. And the science upon which Unity has based its approach is largely untested in humans; scientists have only recently begun to understand the links between senescence and the diseases associated with aging.
The arthritis drug, and senolytic medicine generally, are intriguing, says Salim Syed, the head of biotechnology research for Mizuho Securities USA LLC, and an attendee at the investor conference in New York, but they’re “definitely not a slam-dunk.”
Still, the potential payoff from the company’s arthritis drug ensures investors are watching carefully. After collecting $222 million in venture capital from Jeff Bezos, Peter Thiel, Fidelity, and others on the strength of its preclinical studies, Unity went public last May, raising $85 million in an initial public offering that valued the biotech at $700 million.
David, a biochemist trained at Harvard and the University of California at Berkeley, has founded four other companies, including Kythera Biopharmaceuticals, which won Food and Drug Administration approval for a chin-fat drug before it was bought by Botox maker Allergan Plc for $2.1 billion in 2015. Another, Syrrx, raised $79 million from venture capitalists and was sold to Takeda Pharmaceutical Co. for $270 million in 2005, before winning approval for the diabetes drug Nesina in 2013.
In 2017 researchers funded by Unity published a paper in the journal Nature Medicine demonstrating that removing senescent cells from the injured knees of mice using UBX0101 not only reduced pain, but also prompted the joint to regrow cartilage. The scientists later repeated the finding using human knee tissue removed from patients who’d undergone total joint replacements.
Osteoarthritis of the knee is a painful condition in which the cartilage between the bones wears away. In 2018 there were 725,000 knee replacements in the U.S. If successful, Unity’s drug for the condition could reduce the need for surgery while generating as much as $6.7 billion a year in revenue, according to a recent Goldman Sachs Group Inc. research note on the company.
Last fall doctors began injecting UBX0101 into the knees of older human patients suffering from moderate to severe osteoarthritis. “Right now drugs for knee replacement are pretty ineffective,” says Morgan Stanley biotech analyst Mathew Harrison. “I think the biology is highly interesting, and I think the initial mouse data that they have suggests that there is something to the data.”
Unity isn’t shy about its grand vision of fixing the problem of aging. Last September, when Chief Executive Officer Keith Leonard, David’s longtime collaborator, appeared on CNBC’s Power Lunch, he opined that the science behind Unity’s first drug could be harnessed to treat not just osteoarthritis and vision problems, but also the loss of cardiac and pulmonary function, as well as cognitive function and a wide variety of other “things we have come to accept as part of the normal course of aging.”
Unity’s selection of osteoarthritis of the knee as its first target allows the team to administer the drug locally in the joint and closely monitor how it affects the aged cells around it. Unity announced in January that it’s also seeking FDA approval to begin human testing for a second locally administered drug, UBX1967, that would target age-related eye diseases.
Unity’s “first in-human” data from the knee trials will show whether the drug affects 30 different cellular markers believed to be associated with cellular aging. “It’s a new science,” says Syed of Mizuho Securities. “And it takes a little bit more time for investors to digest new areas of science. So a lot of people are skeptical. But those that are following this are going to look closely at the first in-human data.”
To contact the editor responsible for this story: Dimitra Kessenides at firstname.lastname@example.org, Jeff Muskus
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