Metformin has long been the first-line drug of choice for treating type 2 diabetes. While insulin may be better known (it’s been available since the 1920s), metformin was introduced in the UK in 1958 (FDA approval in the U.S. occurred in 1995), and metformin is now believed to be the most widely prescribed anti-diabetic drug in the world.
More recently, a tantalizing new use for metformin has begun to emerge.
Over the past decade or so, scientists at the University of Texas MD Anderson Cancer Center, UCLA, UC San San Diego, and elsewhere have demonstrated that metformin also has interesting anti-cancer effects under certain circumstances. As MD Anderson researcher Aung Naing put it, “This oldie for endocrinologists is the new kid on the block for oncologists.”
About a year ago, UCLA researchers Richard Pietras and Michael Jung produced some “compelling data” on the use of metformin in mouse models of triple-negative breast cancer and pancreatic cancer, according to David Campbell, a longtime San Diego biotech executive.
“The data have not been published yet,” said Campbell, who has been an entrepreneur-in-residence at San Diego’s Avalon Ventures for the past two years. “The only way one can see the data is to sign a confidentiality agreement with UCLA.”
Nevertheless, the data were promising enough for Avalon and TPG Biotech to co-lead a $15 million Series A investment in Enlibrium, a San Diego biotech founded only about four weeks ago to advance new compounds based on the anti-cancer activity of metformin. San Diego’s Correlation Ventures and Osage University Partners also participated in the deal.
The financing is expected to provide enough capital to advance Enlibrium’s lead compounds through Phase 1 clinical trials. The company also intends to identify biomarkers that could be used to optimize the use of its compounds on various cancers.
Campbell, whose resume includes stints at Phenomix, RQx Pharmaceuticals, Afraxis, Sitari, and others, has taken the helm as Enlibrium’s CEO.
The underlying idea is that cancer cells typically shift into a kind of metabolic overdrive—using inordinate energy to drive the out-of-control proliferation of cancer cells. Campbell explained that with certain cancers, metformin appears to act like a kind of carburetor choke valve that strangles this process.
“Cancer cells are high-performance engines that have a hard time adjusting to a change in the ATP cycle, for example,” Campbell said, referring to the role adenosine triphosphate plays in transporting chemical energy within cells. In the presence of metformin, Campbell said some cancer cells “end up in a state of energetic crisis, and they go into apoptosis,” or programmed cell death.
Scientists have shown that metformin can reduce this energy consumption by cancer cells. But studies also show the effects are limited to a small number of cancers that express specific “transporter proteins,” which open pores through the cellular wall and enable metformin to enter the cell.
Cancers that do not produce such transporters are more impervious, because metformin is not easily absorbed into the cell.
Pietras and Jung recognized that the absence of transporter proteins limited the potential use of metformin as an anti-cancer drug for most cancers, so they designed metformin analogs that overcame such limitations, Campbell said. These analogs showed broad anti-cancer effects in pre-clinical studies that far exceeded metformin, but also maintained metformin’s safety profile.
And because metformin is so widely used as an anti-diabetes drug (and has been used for decades), its safety profile is well understood, Campbell added.
Enlibrium said it has signed an exclusive license for the technology developed in the Pietras and Jung labs. Jung, a distinguished professor of chemistry and biochemistry at UCLA, also contributed to the development of the prostate cancer drugs Xtandi from Medivation and ARN-509 from San Diego’s Aragon Pharmaceuticals (acquired by Johnson & Johnson in 2013).
In conjunction with the financing, Avalon partner Jay Lichter and Heather Preston, a TPG partner and managing director in San Francisco, have joined Enlibrium’s board. The biotech has taken space in COI Pharmaceuticals, the “community of innovation” that Avalon established in San Diego to provide resources and support for the firm’s portfolio of early stage biotechs.