It was only partially in jest that I recently noted Unity Biotechnology as a financial institution with a sideline in rejuvenation research, specifically the targeted destruction of senescent cells. The principals have raised a truly enormous amount of funding in the past year and a half, and recently filed for IPO. They have not yet presented even preliminary human data. Typically the ordering of these matters tends to be at least a little different; there are some raised eyebrows in the community. But if the Unity Biotechnology founders can raise the funds and use them well to advance the state of the art, then more power to them. From their SEC filings we know a little more than we did as to the specific classes of pharmaceutical developed at the company, or at least those they are prepared to talk about today. One is the line of development that started with Bcl-2 inhibitors such as navitoclax, and the other is a more novel approach to senescent cells, one that is as much about suppressing their harmful signaling as it is about destroying the cells.
In using pharmacological methods, Unity Biotechnology has an approach to senescent cell clearance that is objectively worse than, say, the programmable gene therapy pioneered by Oisin Biotechnologies. Pharmaceutical approaches are slow and expensive to tinker into better shape when they turn out to be overly tissue specific or have problematic side-effects. Nonetheless, it is entirely possible to build an enormous business on the back of a first generation senolytic pharmaceutical, because if it clears even 25% of senescent cells from just a few tissue types it will still be far more useful than any other class of medication for inflammatory, fibrotic, and other age-related diseases of those tissues. But the competition in the form of Oisin Biotechnologies will arrive in the clinic a couple of years later with a form of therapy that can destroy all senescent cells in all tissues, and that can be adapted quickly and at low cost.
The Unity folk know this, and the potential market is so very large (every human being much over the age of 40) that I think it probably won't dent their success all that much. There will be many enormous companies and many senolytic therapies coexisting in that market. It is plausible that the more interesting challenge for the Unity Biotechnology staff is to create a therapy that is meaningfully better than the dasatinib and quercetin combination, better enough to justify the very large cost multiple that the company will have to charge in order to keep their investors satisfied. Dasatinib is out of patent protection, its pharmacology is very well characterized in humans, and it runs to a $100-200 cost for a single dose that would be usefully taken perhaps once a year at most. Should the human studies, such as those running at Betterhumans, show it to be effective, that may cause issues for Unity or any other small molecule development concern. None of the other candidate drugs have yet done much better than dasatinib and quercetin in animal studies. The existence of dasatinib will drag down the prices it is possible to charge for anything that performs in the same class - which so far is everything, to a first approximation.
The idea behind Unity - preventing aging - sounds crazy, but it's backed by dozens of scientific papers. There are aging cells, called senescent cells, that build up throughout the body and contribute to what we think of as old age-things like achy joints, waning vision, even perhaps Alzheimer's. Kill those senescent cells with drugs, Nathaniel David reasons, and people might be able to grow old without becoming infirm. "Like, how awesome would it be? The problem is you have to take the first baby step to demonstrate it's possible. That's what chapter one is: demonstrate in a human being that the elimination of senescent cells takes a heretofore inescapable aspect of aging and can either halt it or reverse it." Unity's chief executive and chairman, Keith Leonard, 56, interrupts. "Just that. It's easier to talk to the FDA about treatment of a disease once it's diagnosed than it is to work really early and prevent disease. But prevention is what we'd love to get to."
It's an amazing goal, backed by great science, not to mention $222 million in venture capital and $85 million raised from a May initial public offering, which valued Unity at $700 million, flat with its last fundraising. When a medicine is just beginning human tests, the odds it will make it to market are 10%. But David's career has turned into a blueprint for success in biotech, transforming ideas from university laboratories into viable companies, investment gains and, maybe, drugs. David's five companies have raised $1.5 billion and made investors close to $2 billion without ever actually turning a profit. "He's probably the best person in the world at finding great academic science and shaping it into a fundable story and a sellable business plan," says Kristina Burow, managing director at Arch Venture Partners. She has known David since he was in graduate school and has backed four of his startups.
The idea for Unity arrived in David's email inbox in 2011, from multiple senders at the same time. Jan M. van Deursen had genetically engineered mice so that many types of senescent cells would die. The results of this experiment and of others that followed were striking. Van Deursen introduced David to Judith Campisi, at San Francisco's Buck Institute, who had helped establish the senescent-cell field. Arch founded Unity in 2011, with Van Deursen and Campisi as cofounders. For five years the company didn't even have offices; all the work was done at the scientists' labs.
There's a good reason for the skepticism, no matter how cool Unity's science is: Investors have been hoodwinked by antiaging science before. In 2007, a company called Sirtris went public based on the hype around antiaging compounds related to red wine. GlaxoSmithKline bought Sirtris for $720 million in 2008, but it never resulted in any drugs and was shut down in 2013. Unity needs to show that a medicine can have a clear effect in humans. Its first attempt, UBX0101, will target arthritis. Now, in the first human test, it will be injected into the knees of 30 patients, who will fill out surveys about how much pain they feel, have fluid removed from their knees and undergo MRI scans. They'll be compared with ten patients who will get a placebo injection. Any signs that the drug is making patients better will be seen as a reason to move into further studies. Unity expects to enter two more drugs into human studies by the end of next year. Candidate diseases include glaucoma, where killing senescent cells seems to lower the pressure that builds up in the eye, and lung diseases, where it may coax lung cells to stop making scarred, fibrous tissue.
Unity has raised so much money precisely because its executives know it may take multiple tries to find a medicine. It's not known what the risks of killing senescent cells are; it's possible they could include, for instance, slow wound healing. There's no way to know until human tests begin.