A little more than a year after completing the sale of his company to Amgen Inc. in a $10.4 billion deal, the former CEO of Onyx Pharmaceuticals Inc., Tony Coles, is back in the biotech game, this time heading start-up Yumanity Therapeutics, which is aimed at neurodegenerative diseases and already boasts a potential new target for Parkinson's disease. (See BioWorld Today, Aug. 27, 2013.)

It's an opportunity that came about thanks to his "very old and dear friend" Susan Lindquist, whose pioneering work in protein misfolding previously founded Foldrx Pharmaceuticals Inc., a rare disease firm snagged by Pfizer Inc. in 2010. In fact, Coles and Lindquist met while serving on Foldrx's board.

"I gained immediate respect for her science, which is world class," he said of Lindquist, who works at the Whitehead Institute at the Massachusetts Institute of Technology and is a 2009 National Medal of Science winner. Coles said he also was impressed with Lindquist's "values, ethics and integrity," so when she contacted him several months ago about establishing a company around the technology in her lab, "I told her I would give her a hand."

At first that was to entail setting up the firm and raising money, but "the more I studied the technology, the more compelled I was" to take a bigger role, he said.

A large part of the attraction was the technology itself. Yumanity's discovery platforms comprise technologies to model and screen compounds in pathologies of protein misfolding, believed to underlie nearly all neurodegenerative diseases. A protein's amino acids must fold in a particular way to ensure proper cellular function; misfolded proteins, on the other hand, "can really wreak havoc in the cellular processes," Coles said.

"Once that goes awry, it's really hard to get the cellular processes back on track," he added, with the result being the clumping of proteins by cells that have been damaged – beta-amyloid in Alzheimer's and Lewy bodies in Parkinson's, for example.

The trick has been finding methods of studying those pathologies and testing compounds in ways that can be translated from the lab to humans. The "beauty" of Yumanity's approach is that it involves a phenotypic rather than a target-based approach, Coles said.

Yumanity's ultra-high-throughput phenotypic screening platforms are designed to model protein misfolding pathologies in yeast, then testing compounds "to see if you can rescue the yeast," he explained. Then those compounds are tested in the firm's stem cell-derived neuron platform, again, to see if those cells can be rescued. If they can, "then you know you have a compound that has biological activity," he told BioWorld Today.

So far, the company already has taken those "two very promising steps" in Parkinson's, having identified a potential new target and is looking to advance a chemical series against it. Coles said it was too early to talk about clinical time frames – "we'll let the science lead us" – but Yumanity, which currently has five employees in addition to its CEO, is expected to grow its headcount to as many as 20 or 25 by the end of 2015.

The company was seeded by Coles – who walked away from last year's Onyx deal with nearly $60 million, according to SEC reports – and Lindquist. It will seek to close a series A financing round in the first quarter of next year.

'THE PROBLEMS OF THIS MILLENNIUM'

Along with the technology, it also was the focus on neurodegenerative diseases that drew Coles' interest. Yumanity also plans to focus efforts in Alzheimer's disease and amyotrophic lateral sclerosis (ALS).

"These are the problems of this millennium," he said, adding that an estimated 50 million people worldwide suffer from neurodegenerative disease. Costs for treating those diseases run about $650 billion are expected to triple by 2050, "so we have a moral imperative."

Indeed, the company's name itself is intended to reflect that imperative. Combining "humanity" with the "y" in "yeast," it's intended to reference the firm's "yeast to human" technology. But it also refers to a "problem so big, so intractable and [one that] costs so much, that we just have to do something," Coles said.

Currently, there are no disease-modifying therapies approved, though it hasn't been for a lack of trying. Drug development in the neurodegenerative space has been riddled with devastating failures. The past couple of years alone have seen clinical misses in Alzheimer's with crenezumab, an anti-amyloid beta antibody from AC Immune SA and Roche AG, and in ALS with Cytokinetics Inc.'s tirasemtiv and dexpramipexole, a drug developed by partners Biogen Idec Inc. and Knopp Biosciences LLC. (See BioWorld Today, Jan. 4, 2013, April 28, 2014, and July 17, 2014.)

Coles and his team, however, remain undaunted by the space's reputation for difficulty.

"A lot of people said the same thing in the 1990s [about HIV]," he noted. Now HIV is down to a chronic, manageable illness. "Great things come out of some out-of-the-box thinking."

Nor is he daunted by the prospect of running his first start-up. His resume includes stints at Bristol-Myers Squibb Co., Vertex Pharmaceuticals Inc. and NPS Pharmaceuticals Inc. prior to taking the helm at Onyx in 2008 – in addition to the Amgen acquisition, his tenure at Onyx included the purchase of Proteolix Inc. for multiple myeloma drug that would gain approval as Kyprolis (carfilzomib) and reaching a favorable end to a long-running dispute with partner Bayer AG over a next-generation multikinase inhibitor – but Yumanity will be Coles' first foray into heading up an early stage firm. (See BioWorld Today, Oct. 13, 2009, and Oct. 13, 2011.)

Because of his Onyx experience, "I do actually know what success looks like," he said. "So we'll work backward, using that as a template."

Joining Coles on the executive team is Kenneth Rhodes, who will serve as chief scientific officer, who will oversee the work on Yumanity's integrated platforms, which were developed in close collaboration with scientific co-founders Vikram Khurana, Chee-yeun Chung and Daniel Tardiff.