Novato startup Unity Biotechnology tackles arthritis, glaucoma
In biotechnology, sometimes a CEO's personal pain motivates scientific gain.
Osteoarthritic pain in Nathaniel "Ned" David's toes serves as a personal driver for the Unity Biotechnology First Company that he quietly co-founded in 2011 and then in February 2016 propelled into the public arena from its home at The Buck Institute for Research on Aging in Novato. A runner for some 35 years, David sees the potential that a drug under study at his fledgling company might eventually ease or eliminate the pain.
'We have made a lot of progress over the last few years,' said David, 49, Unity's CEO, who earned a Ph.D. in molecular and cellular biology at University of California, Berkeley. Early drug candidates at the company may target arthritis and glaucoma. 'Osteoarthritis is the primary reason it hurts to be old. Imagine if it didn't hurt to be old,' he said.
Unity Biotechnology has initial funding from venture investor ARCH Venture Partners, with additional capital from Venrock, WuXSi, Mayo Clinic and Unity's management team. With an initial staff of 21, the company will look for drugs to counter cellular senescence, the process where cells cannot replicate but remain alive and contribute to diseases of aging. By the end of next year, the employee count will likely grow to 50.
Fighting for lives
Many of the company's scientists, including collaborators in places such as Mayo Clinic, are in their 30s. 'Technical success can materially impact all of their lives in a real way. There's an urgency that people feel here. They are literally fighting for their lives,' David said.
'Our investors could fund us forever if we wanted,' David said. 'We take the money as we need it. We're not talking about the money part. We will make an announcement mid-year on money.'
He put his own money into the venture. 'I put a lot of capital into this,' he said, investing profits he made from previous biotech ventures, such as Achaogen, Syrrx, acquired by Takeda Pharmaceutical, and Kythera Biopharmaceuticals, acquired by Ireland-based Allergan in October 2015 for $2.1 billion.
'Since Kythera (which he founded) I don't do stuff for money anymore,' he said. 'You saturate pretty quickly. Additional money has no impact on your happiness. Things that make me happy are: seeing my 7-year-old son really happy; experiments working; seeing people get off on the collective metaphor of the company, feeling that electricity. Those are things that move me. I would really like it if my osteoarthritis went away so I could go for a 10-mile run and not worry that the next day I would be in pain.'
ARCH and Venrock hold major stakes in biotech investments. 'In the last bubble, ARCH created some $25 billion in capitalization of companies. Venrock was' not quite that big, David said. 'Those are our two funders. We will probably bring in some others.'
Revenue from an approved drug to clear senescent cells, if achieved, could be 10 years away, he said.
'We have lots of evidence that these cells are driving disease,' David said about glaucoma and arthritis, and that elimination of senescent cells halts the disease.
Senescence causes inflammation
When genetic mutations damage human cells, one of two things normally occurs: they die in a process called apoptosis then are reabsorbed or recycled by the body; or they become senescent, where they stay alive but lose their ability to repair or regenerate. Both processes suppress tumors, and serve as the body's usually successful mechanism to halt cancer early in life.
Researcher Leonard Hayflick discovered senescence in the 1960s, and found that human fetal cells only divide 40 to 60 times before they become senescent. But the process, beneficial early in life, turns destructive in later years. Senescent cells secrete about 40 proteins; some cause inflammation.
Transient inflammation induced by senescent cells can help ward off invading organisms after an injury, indicated by redness and swelling that attends a wound in early healing stages. Senescent cells also produce growth factor that helps close a wound. But chronic inflammation from clusters of senescent cells contributes to many diseases of aging — ironically including cancer.
In apoptosis or cell death, enzymes dissolve proteins and DNA. Human bodies are 'basically insoluble, which is why it's safe to take showers,' David said. The enzymes in apoptosis make the insoluble elements in cells soluble. 'It's like the ultimate form of giving in to entropy,' he said.
'Senescence is uniquely druggable,' David said, with drugs that push senescent cells to die by apoptosis. That makes senescence an attractive scientific realm in which business interests can grow, possibly into a mammoth market that could help billions of people fend off maladies of aging. Even a modestly priced drug could reap immense revenue and potential profit.