DUBLIN – Black Diamond Therapeutics Inc., the latest startup to emerge from the Versant Ventures stable, raised $20 million in a series A round to progress a novel platform for tackling a category of cancers that earlier generations of targeted therapies have failed to address.
The new venture has been in stealth mode for some time and already has five active programs, including three that have progressed through lead optimization or are in IND-enabling studies. A first clinical trial could happen by 2019 or 2020.
Although it is not yet disclosing the science underlying its target discovery platform, Black Diamond has big ambitions. It aims to haul the old targeted therapy paradigm into the computational biology era, by identifying and targeting what it claims is a whole new category of cancer-causing genes, which it terms "allosteric mutant oncogenes."
"We're taking unactionable mutations and rendering them actionable – that for us is the guiding principle," CEO and co-founder David Epstein told BioWorld. In other words, the company aims dramatically to expand the druggable oncogenome.
Epstein, the former chief scientific officer at OSI Pharmaceuticals, is intimately acquainted with the strengths and the weaknesses of traditional tyrosine kinase inhibitors. So, too, is his co-founder, Elizabeth Buck, who is executive vice president for discovery and translational sciences at Black Diamond. She was a senior pharmacologist at OSI and was centrally involved in the development of its flagship drug, Tarceva (erlotinib), the EGFR inhibitor that gained FDA approval in 2004 for treating non-small-cell lung cancer (NSCLC) and a year later for treating pancreatic cancer. Tarceva's commercial success – fueled by its approval in 2010 as maintenance therapy for advanced NSCLC – prompted OSI's $4 billion buyout by Tokyo-based Astellas Pharma Inc. in 2010. (See BioWorld Today, May 18, 2010.)
Tarceva and other drugs targeting the four-member ErbB family of receptor tyrosine kinases were designed to do a specific task – act on mutations located in the receptors' kinase domains. "This is a market that is incredibly robust and incredibly important," Epstein said. Yet they work only in limited patient populations – and the biological reasons for the variations in response to therapy are not always clear.
Certain infrequent mutations have long been associated with a lack of response or with resistance, but drug developers did not dig any deeper into the underlying biology. "They were sort of ignored and shrugged off," Versant partner Alexander Mayweg told BioWorld.
It's a problem that Epstein has been quietly working on for some time. He and Buck conducted an extensive set of studies involving, Epstein told BioWorld, every ErbB inhibitor they could lay their hands on, including approved and investigational drugs. They screened those against a panel of ErbB mutations known to be associated with a lack of response to therapy and probed the underlying biology.
"That led to the astounding conclusion that these were not only transforming but resistant," Epstein said.
That effort has provided the foundation for a platform that can predict which lesions outside the kinase domain of an oncogene lead to an allosteric activation mechanism.
The company has not yet disclosed any structural or mechanistic data to support its conclusions – it plans to publish some papers next year, Epstein said – but it is capable, he added, of targeting "baskets of mutations" with a single agent or drug class. The chemistry effort to address those targets is considerable – there are no existing agents or drugs that are suitable to the task. "The chemistries to get at drugs to target these are unique," he said. And the basic observation should be extended to other disease-associated proteins that are capable of undergoing large-scale conformational change.
Black Diamond is the first company to undergo incubation at Versant's Ridgeline discovery engine in Basel, Switzerland. The Californian VC has sprinkled several such centers across the globe, in order to tap into drug discovery and development expertise in various locations. It now has wet lab facilities in San Diego, Toronto, New York and Basel, which collectively employ 80 to 100 scientists at a given time. The number fluctuates as some staffers move into the startup projects they work on. "It's a fluid model," said Mayweg.
As well as its Basel base, Black Diamond is opening a computational biology and structural biology facility in Toronto, but it will ultimately locate its headquarters in the Boston area, Epstein said. The company and Versant are already working on a larger venture capital round, which they aim to conclude next year.