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After Spinning Onyx into Gold, Coles Returns to Lead a CNS Startup

Xconomy Boston — 

Tony Coles could easily be on a beach sipping mai tais right now. You can plan for an early retirement in biotech when you turn two different companies around and steer the latest one of them into a $10 billion buyout.

But the 54-year-old Coles, who helped restructure NPS Pharmaceuticals and then lead Onyx Pharmaceuticals to a sale to Amgen last year, is showing that he has no plans to kick back and call it a career. He’s come out of a year-plus hiatus today to announce his latest move—and it’s not the sort that you’d expect from someone used to either working at, or running, large companies with drugs either on the market or in clinical trials.

Instead, Coles is taking on an entirely new challenge. He’s going from the Bay Area to the East Coast, and leading a brand new startup called Yumanity Therapeutics that’s launching today in Cambridge, MA. Yumanity intends to tackle some of the most notoriously difficult to treat neurological disorders—like Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s Disease, and Parkinson’s Disease.

Coles is a founding investor in Yumanity and its chairman and CEO. He formed the company with scientific founder Susan Lindquist, with the goal of treating diseases caused by protein misfolding—when a mistake occurs in the complicated origami that turns a long linear chain of amino acids into a functional, three-dimensional protein. The company claims that an in-house proprietary platform has unearthed a potential new drug target for Parkinson’s. It’ll start out advancing a potential drug for the condition, while trying to identify lead compounds for Alzheimer’s and ALS.

Developing treatments for these diseases, of course, has historically been difficult. Many companies have tried and spectacularly failed to do so—in part because the underlying biology of what’s really going wrong in these patients isn’t crystal clear. But Yumanity believes its drug discovery platform—which utilizes three integrated methods, including testing drug candidates against stem-cell-derived neurons—might give it a chance to succeed where so many have failed.

These drug discovery methods came from Lindquist’s lab at the Whitehead Institute and the Howard Hughes Medical Institute. They were developed by Lindquist and Yumanity’s other scientific co-founders, scientists Vikram Khurana, Chee-yeun Chung, and Daniel Tardiff—all three will leave their posts at Massachusetts General Hospital and the Whitehead to join Yumanity full-time. Former Biogen Idec neurology executive Kenneth Rhodes is Yumanity’s chief scientific officer.

Tony Coles, CEO of Yumanity Therapeutics

Tony Coles, CEO of Yumanity Therapeutics

“[O]ur unique approach overcomes the fundamental limitations of today’s target-based drug discovery by exploiting the power of phenotypic screening in yeast and human stem cell-derived neurons,” Coles said in a statement. “This approach is the Yumanity advantage and enables us to identify potential new therapies to modify the cause of these diseases at the cellular level.”

The move is a big departure for Coles. He’s a clinician by training who made the move to industry in the early ’90s, rising through the ranks at large pharmaceutical companies like Merck and Bristol-Myers Squibb before switching over to biotech just after the turn of the century. He spent three years as a commercial executive at Vertex Pharmaceuticals before moving on to Bedminster, NJ-based NPS Pharmaceuticals (NASDAQ: NPSP) in 2005. He was named CEO the following year. NPS was then a developer of osteoporosis drugs, and shortly after Coles came aboard, the FDA rejected its lead drug, known as Preos, and asked for another clinical trial—one the company couldn’t afford. Coles and Francois Nader (who would succeed him as CEO) then helped engineer a massive restructuring at NPS, cutting costs and slashing the company’s workforce significantly. Coles left in 2008 to run Onyx, and handed the reins at NPS to Nader; NPS has since gone on to reshape itself as a developer of orphan drugs, and won FDA approval of its first product in 2012.

It’s at Onyx that Coles enjoyed his biggest success, however. He came aboard the company in 2008 to a less than stellar reception from investors. But Coles took some risks and essentially turned Onyx from a half-a-product company—one that only drew cash via a revenue split Bayer on the cancer drug sorafenib (Nexavar)—to one with three different drugs on the market.

For one, under Coles’s watch, Onyx fought and won a legal dispute with Bayer ensuring it would retain a share of sorafenib’s revenue in the case of a buyout, and a 20 percent royalty stream to a next-generation version of sorafenib called regorafenib (Stivarga) that was approved by regulators in 2013.

Coles also made a shrewd call in 2009 to buy Proteolix for $276 million up front and $811 million overall. Proteolix was developing a cancer drug called carfilzomib that was in mid-stage trials at the time. The move wasn’t popular with investors, who wanted to see Onyx focus its resources on maximizing sorafenib—not diversifying and taking on a risky project.

“We knew we couldn’t be a one product company,” Coles told Luke Timmerman in an interview with Xconomy a few years ago. “It took courage, because buying an untested asset is a scary thing. It’s daunting. The question I posed to our team on the eve of the acquisition was not one of business judgment. It was one of courage.”

But the deal was a winner for Coles. Carfilzomib went on to win FDA approval as a treatment for multiple myeloma. Called Kyprolis, it was the biggest reason Amgen (NASDAQ: AMGN) bid $125 per share, or around $10 billion, for Onyx in August 2013. Coles reportedly pocketed more than $50 million from the buyout.

Coles’s move to Yumanity is reminiscent of the one Deborah Dunsire made to Forum Pharmaceuticals last year. Just two months after abruptly stepping down as the head of Takeda’s Millennium Pharmaceuticals unit in Boston (a division that has since scrapped the Millennium name), Dunsire became the CEO of a Watertown, MA-based startup then called EnVivo Pharmaceuticals, which is similarly developing treatments for neurological disorders.

The big difference? EnVivo, now known as Forum Pharmaceuticals, already had a drug in mid-stage trials when Dunsire came aboard. Yumanity is essentially starting from scratch.

“I am thrilled and inspired to be at the forefront of innovation in an area of real, global medical need,” Coles said in today’s statement. “We believe the time is now to translate the remarkable advances in protein folding science achieved by Sue and her colleagues into a drug discovery engine that we believe can have a rapid and transformational impact on neurodegenerative diseases.”