Live longer? How about starting with healthier knees or clearer eyesight?
That’s the proposal from Unity Biotechnology, unveiling itself today with drug programs based upon research into a biological process that, when left undisturbed, seems to hasten aging.
Based in the San Francisco Bay Area, Unity wants to interrupt that process—not to tap into a fountain of youth but to go after a set of more real-world problems, at least at first, such as osteoarthritis and glaucoma. The firm is also trying to ride the buzz around anti-aging by using terms like “diseases of aging” and “lengthen health span.”
Is there really a connection between fixing knees and eyes and making people live longer? In a paper published today in Nature, Jan van Deursen of the Mayo Clinic in Rochester, MN, and colleagues described how killing cells that have fallen dormant, into a state called senescence, prolonged the life of male and female mice by 17 to 35 percent and reversed several disease states. Unity has license to the work.
That’s wonderful for the mice, but major caveats apply since the work has not yet progressed to humans. Human cells also go into senescence, to be sure. It’s widely thought to be a protective measure against cancer. If there’s risk of a cell turning cancerous, because of rapid division or stress such as radiation, it goes dormant. As we get older, senescent cells accumulate in various niches of the body. Although dormant, they continue to emit proteins that can contribute to inflammation, which is linked to a wide range of diseases.
Unity is going to test the theory that killing these cells in specific locations, like the knee joint or the eye, will treat specific diseases. In osteoarthritis of the knee, for example, the theory is that senescent cells produce chemicals that block other cells from building cartilage. Kill the senescent cells and perhaps the cartilage will regrow, says CEO Nathaniel “Ned” David (pictured), who has helped found several biotech companies including the antibiotic maker Achaogen (NASDAQ: [[ticker:AKAO]]) and the cosmetic drug firm Kythera Biopharmaceuticals.
“I have a strain of practicality,” said David. “Choose a disease, dose it locally, cure it. Then go after something amazing like health span.”
Unity plans to use traditional small molecule drugs to kill the cells, says David, who has been working under the radar for four years to build the company. He was inspired by previous work from van Deursen and from Judith Campisi, a professor from the Buck Institute for Research on Aging. Campisi is a Unity cofounder, and the company is based near the Buck in Novato, CA, about 45 minutes north of San Francisco.
As Campisi outlined in a 2011 paper, attempts to wipe out senescent cells will have to take into account the benefits the cells seem to have, as well, on tissue repair and wound healing.
Van Deursen, who is also a Unity cofounder, and his colleagues addressed those concerns in the paper published today. In their experiments, killing senescent cells in mice did not seem to have serious side effects on tissue repair. Still, Unity scientists will pay close attention if and when their drugs are tested in humans.
The connection between senescent cells and inflammation suggests killing them might help fight all kinds of disease, including Alzheimer’s and autoimmune conditions. But Unity is keeping its focus narrow for now, with two of its most advanced programs aimed at fixing the joint pain of osteoarthritis and the eye disease glaucoma, which can lead to blindness if left unchecked. Unity is also interested in atherosclerosis, the buildup of fatty plaques in the arteries. Those are all diseases of aging, one could argue, but if that makes Unity an anti-aging or lifespan-extending company, then most drug companies could fall under the same rubric.
A Unity press release tried to frame the company as a competitor to Calico Labs, the wholly-owned subsidiary of Alphabet (formerly known as Google) that has attracted top drug and biomedical people such as former Genentech CEO Art Levinson and University of California San Francisco researcher Cynthia Kenyon. When pressed on the comparison, Unity CEO David and others shied away to some extent, in part because there’s little information about what Calico is actually working on, other than saying it’s “tackling aging.”
But David did say this: “We intend to publish a lot, be intellectual leaders, and host meetings, in contrast to others in the space who are sphinx-like.”
I asked Calico representatives for a comment on Unity and the Nature paper from van Deursen. They did not respond by press time.
Unity’s main venture backers are Arch Venture Partners and Venrock. Arch’s Bob Nelsen said the firm has raised small two rounds of funding already and is seeking a much larger round this year. He declined to give specific amounts.
I asked why Unity’s financial profile differs from that of Juno Therapeutics (NASDAQ: [[ticker:JUNO]]) and Denali Therapeutics, two startups backed by Arch that raised huge amounts of cash out of the gate. Arch’s Kristina Burow, who sits on the Unity board with Nelsen, said Unity is much earlier stage than those two were and didn’t need a ton of cash. “It just needed to show that [the senescent cells] were a druggable biology,” Burow says.
That has been accomplished, she says. Unity is now developing drugs to hit four different targets. The firm has also brought on three executives since the end of 2015: Jamie Dananberg, formerly of Takeda Pharmaceutical and Eli Lilly, is chief medical officer; Dan Marquess, previously at Theravance Biopharma, is chief scientific officer; and former Kythera CEO Keith Leonard is executive chairman.
Leonard, Venrock’s Camille Samuels, and David round out the Unity board.
Leonard and David worked together previously at Kythera. Allergan bought Kythera for its cosmetic
