A new cancer immunotherapy company has spun out of Stanford University with backing from a quartet of venture investors and a big hand from the taxpayers of California.
The Palo Alto, CA-based firm, dubbed Forty Seven, emerged Wednesday with a program already in clinical trials, a rarity for an academic spinout. Stanford researchers led by Irving Weissman, the director of the school’s Institute of Stem Cell Biology and Regenerative Medicine were able to begin testing the drug in humans thanks to $30 million in funding from California’s stem cell agency, known as CIRM.
“Instead of having to form a biotech company too early,” Weissman says, he and colleagues formed a team, hired outside consultants, and ran their experiments at Stanford. With weekly team meetings, “we could avoid the kinds of mistakes and miscommunications and overcautious risk aversion that occurs in every biotech or pharma.”
But now the work is indeed part of a biotech. Starting with a $75 million Series A war chest, Forty Seven has licensed a suite of intellectual property from Stanford and is taking the reins of the two Phase 1 trials now underway, with plans to start several more trials in 2016 and 2017, according to chief business officer Craig Gibbs.
The round was led by Lightspeed Venture Partners and Sutter Hill Ventures with participation from Clarus Ventures and GV, formerly known as Google Ventures. (Forty Seven is named for the CD47 protein on tumor cells that its experimental cancer drugs aim to attack.)
This is the kind of news CIRM has yearned for in recent years: significant private cash that gives CIRM-funded projects a push to become actual products and to return value to the state. The agency, officially the California Institute for Regenerative Medicine, recently went through an overhaul, branded as “CIRM 2.0.” After a decade of funding buildings, salaries, and early stem-cell related research—not to mention conflict of interest problems that included a past CIRM president and a different company with Weissman’s imprimatur—CIRM and its new president acknowledged it needed to show results for the $6 billion taxpayers committed to the agency in 2004.
“This type of follow-on funding is what we’re looking for,” says CIRM spokesman Don Gibbons, who adds that the big financial awards for Stanford were in line with the agency’s mission “to get things moving early when others won’t invest.”
Including the $30 million for Weissman’s CD47 antibody work, Stanford has received more than $300 million from CIRM, including funds to build the new headquarters of Stanford’s stem cell research.
Forty Seven’s Gibbs, who spent more than 20 years at Gilead Sciences (NASDAQ: [[ticker:GILD]]), says it’s rare for an academic group to take a drug program all the way into the clinic. “It was remarkable what Irv and his colleagues were able to achieve using CIRM funding in an academic setting. Universities aren’t built for that.”
One trial began in 2014 to test the lead drug, known for now as Hu5F9-G4, in patients with solid tumors. A second trial began late last year in patients with acute myeloid leukemia that has either recurred after treatment or has not responded to treatment.
Hu5F9-G4 is a monoclonal antibody that attaches to the CD47 protein on cancer cell surfaces and prevents the cells from hiding from the patient’s immune system.
That might sound familiar to those who follow cancer immunotherapy. The first drugs of their kind to gain regulatory approval have also been monoclonal antibodies that help unmask tumors. These drugs, called checkpoint inhibitors, go by the names ipilumumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda), and have been effective for certain types of skin and lung cancer. They engage with tumor cells and draw the attention of T cells, the immune system’s main attackers.
But Hu5F9-G4 aims to unmask tumors in a different way. It attaches to tumors and draws the attention of macrophages, part of the innate immune system—the body’s first responders, whereas T cells, part of the adaptive immune system, are more like the special forces called in for precision attacks. Calling in macrophages to eat tumor cells that display CD47 might seem too blunt an instrument, because CD47 is also produced by normal cells. Simply flagging any CD47-producing cell for destruction could lead to a lot of collateral damage.
But cancer cells also produce what Weissman and colleagues call an “eat me” signal from a protein called calreticulin. Normal, healthy cells don’t. By cutting off the CD47 “don’t eat me” signal, Hu5F9-G4 should in theory allow the calreticulin signal to prevail. One side effect to watch for is anemia, because old but healthy red blood cells
