comparative genomics, which can be used to look at the expression of different genes in different disease states to help find novel drug targets. This is a “very well trodden” method of discovery, according to the VC.
“I believe in the ability of such systems to help identify potentially interesting targets, but historically, there is no support for decades of claims that any new target ID or rational design technology really cuts development time in a systematic, across the board way,” the VC says. “Like any other ‘omics’ technology, output is all dependent on inputs—which are, by definition, flawed since our knowledge base is always limited—and processing of the data.”
Narain counters that his system’s confluence of technologies, such as its ability to combine information on lipids, metabolites, and other markers, gives it a more complete picture of biology than others. And he contends that a pharma company would have spent $500 million to get where Berg is today (though he won’t specify how much Berg has actually spent comparatively). The onus is on Berg, then, to back up the claims, not just by efficiently producing drug candidates and validated biomarkers, but by creating therapies that make a difference.
So far, hints that Berg’s system could produce viable treatments come from petri dish and animal studies, and small early human trials. Narain says, for example, its platform predicted that its cancer drug candidate would reverse what’s called the Warburg effect, meaning by changing the fuel a cancer cell depends on—making it use up more oxygen and less glucose—it could cause that cancer cell to behave like a normal, healthy one. The platform similarly led it to a potential diabetes drug that might be able to stabilize glucose levels, and biomarkers that might be able to predict heart failure or prostate cancer, he says.
Still, that’s nowhere near enough to set the biotech world—which is in the midst of seeing a new generation of cancer immunotherapies charge through late-stage studies—abuzz. What might make waves for Berg is its BMP31510, which is currently in Phase 1b testing.
BMP31510 is a proprietary engineered formulation of ubidecarenone, a coenzyme found in mitochondria that helps produce energy within the cell. Narain says what the company has seen in early testing is that the molecule is able to “shift” the metabolism of a cancer cell, normalizing its function. The idea of messing with the metabolism of cancer cells brings to mind Cambridge, MA-based Agios Pharmaceuticals (NASDAQ: [[ticker:AGIO]]), which essentially tries to starve cancer cells to death, but Narain notes that Agios is focused only on the range of cancers with certain genetic mutations like IDH1 and IDH2.
“We’re looking at the entire system and saying our drug shifts the metabolism of any cancer cell,” he says. “We’re not cancer specific—this is a broad-spectrum mechanism.”
One potential challenge for Berg is the fact that ubidecarenone is already widely marketed as a nutritional supplement, often under the names coenzyme Q10 or CoQ10. This means that, as Schadt says, Berg is trying to solve a “pretty difficult problem.” Rather than creating a new, patentable molecular entity and testing it, Berg must figure out how to deliver it at the right time, at the right dose, and over the right span of time, and build intellectual property around that.
“Actually delivering that to a living person and having it be a potent enough to have some therapeutic benefit without killing somebody or adversely affecting them is just a hard, hard game to play,” Schadt says. “That’s where I think a lot of skepticism would come if those on the pharmaceutical side took a hefty look.”
The answers will come soon. Berg is running a four-armed Phase 1b trial testing the molecule in a variety of solid tumors. In some of those arms, Berg is combining the drug with chemotherapy drugs like docetaxel or gemcitabine. In another, BMP31510 is being tested alone. Berg expects to enroll a total of more than 200 patients, and is collecting tissue samples before or after treatment, and doing various imaging studies to track the glucose uptake in patients’ tumors. If it sees some significant responses in patients with certain types of cancer—gastrointestinal, or pancreatic, for instance—it might then break out the patients in those groups and start a Phase 2 study of patients with just those cancers. That could happen by the end of the year, Narain says.
Maybe, by then, there’ll be a much clearer picture of what Berg is capable of.
“I think in the next 12 to 18 months you’ll see significant partnerships come out of what we’re doing,” Narain says.
