Searching for the "master key" that inhibits a family of mutations across different tumor types.
CEO: David Epstein, Ph.D.
Based: Cambridge, Massachusetts
Clinical focus: Developing tumor-agnostic drugs by targeting cancer-driving mutations that have previously been “undrugged and unexplored.”
The scoop: Versant Ventures launched Black Diamond in December 2018 with $20 million to go after an overlooked group of oncogenes, or mutated forms of genes that can drive cancer. A month later, the company picked up another $85 million to move its lead program into the clinic in early 2020.
What makes Black Diamond fierce: Black Diamond is taking cancer precision medicine to the next level by looking beyond the usual suspects. Precision medicine treatments typically drug oncogenes—mutated genes that can drive cancer growth—by targeting kinase domain mutations. But Black Diamond is aiming at another set of mutations that hasn’t been drugged before.
Most kinase inhibitors bind to the same part of a kinase enzyme: the ATP binding site. Black Diamond is interested in a previously unexplored group of mutations, called allosteric mutations, that could be drugged selectively through the ATP binding site. CEO David Epstein, Ph.D., and cofounder Elizabeth Buck, Ph.D., found that they didn’t need to target allosteric mutations individually and that they could group different mutations in the same oncogene into “families” that can be hit with the same drug.
And Black Diamond was born.
It is the first biotech to emerge from the Ridgeline Discovery Engine that Versant set up in Basel, Switzerland, to advance programs originating at European academic centers. It has since moved its headquarters to the biotech hub of Cambridge, Massachusetts.
Though Black Diamond uncloaked in 2017, it had been operating in stealth mode since 2015, working on its MAP (mutation, allostery and pharmacology) platform that identifies, discovers and targets allosteric mutant oncogenes across different genes and patients.
It does this by crunching population-level genetic sequencing data that’s either out in the public domain or available to Black Diamond through collaborations, Epstein said. The tech uses algorithms to rank mutations by how oncogenic they are, or how likely they are to lead to cancer.
“We screen and evaluate those potential oncogenic driver mutations,” he said. “We make tumor models and build programs around that. That’s the platform: we study mutations, show how they work and build programs where the mutation alters drug pharmacology.”
At launch, Black Diamond said it had come up with four programs, two of which had gone through lead optimization or into IND-enabling studies. Two of those programs target allosteric EGFR and HER2 mutations.
“When we talk about allosteric mutations in EGFR and HER2, we’re talking about a family of mutations distributed throughout the protein that behave in a consistent and perhaps convergent manner, and for which we have been able to develop a single ATP site-targeted therapy to inhibit,” Epstein said. Grouping the mutations into families is the critical step because each mutation on its own would be considered too rare to pursue, he said.
“Our lead drug candidate, BDTX-189, inhibits a family of dozens of oncogenic mutations spread across EGFR and HER2. If we looked at individuals, it would probably not be considered economically viable,” he said.
Black Diamond describes this ability as the “master key”—a single drug to inhibit a family of mutations that occur in a single oncogene but in different tumor types.
“It’s how we go from population-level data to a tumor-agnostic study with a single drug to target a set of mutations. We believe you can do this not only in EGFR and HER2, but in other oncogenic kinases as well,” he said.
The company plans to bring its lead program into the clinic in 2020 and continue to build up its computational science chops to dive into databases of mutations and build drug programs. With about 20 staffers, Black Diamond is looking to double in size over the next year or two. But it’s not looking for just anyone.
“We need different kinds of biologists. Traditionally, you could spend your life studying EGFR or HER2. You would look at a few mutations and you would know about HER2 biology. … This is a way to look at the entire oncogene as a potential target class and thinking about the role of mutations in oncogene activation rather than as a byproduct. It really is a way we want people to come in and think about how to develop drugs,” Epstein said.
“The opportunity here is to bring a new class of biologists and chemists who would be trained to think about the effects of those mutations: what these mutations mean for protein function, how nature selected them, how to build programs, what those programs look like and how to get selectivity,” he said. “All those processes require a new lens for looking at how oncogenes work in biology. So, we’re building and looking for people capable of making that kind of transition.”
Investors: The Invus Group, New Enterprise Associates, Nextech Invest, Perceptive Advisors, RA Capital Management, Versant Ventures