Backed by Sofinnova, Joel Martin, Ph.D., and Olivier Laurent, Ph.D., of Dauntless Pharmaceuticals went program hunting last year. But after going to academic groups as well as biotech and pharma companies across the U.S., they started losing hope. That is, until they found their diamond in the rough in Italy.
That diamond, a program targeting the BAG3 protein to treat cancer, is the basis of Martin and Laurent’s new company, Intrepida Bio, which uncloaked with $9.5 million from Sofinnova and Canaan Partners. That funding will bankroll IND-enabling studies for antibodies that target BAG3 and its receptor IFITM-2, which normally plays a role in the immune response against viruses but is hijacked by tumors to create an environment that promotes their growth and thwarts attacks from the immune system.
“Usually, as we dug into assets over the course of the year, we started out excited but got less excited. This was the opposite. The further we dug into the data, the more enthusiastic we became, in part because of multiple layers of validation to this technology,” said Martin, president and CEO of both Dauntless and Intrepida, to FierceBiotech.
The University of Salerno spun the technology out into Biouniversa, which developed and validated it under the leadership of Maria Caterina Turco, a professor at the university. Turco’s team showed both in lab dishes and animal studies that the anti-BAG3 antibodies slowed tumor growth, cut down on metastases and boosted survival, Martin said. Those studies included those carried out in pancreatic cells from mice and humans.
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Pancreatic cancer would be a natural focus for Intrepida, as “it's where we have the most data at present,” Martin said, and it remains a deadly, difficult-to-treat cancer with five-year survival rates in the single digits.
Turco’s team at Salerno also found in a 2012 study that all 346 patients whose pancreatic tumors they analyzed expressed BAG3 in the tumors, but not in the surrounding healthy tissue. This type of pancreatic cancer, pancreatic ductal adenocarcinoma, makes up 85% of pancreatic cancer cases and is still treated with cytotoxic cocktails.
“There are the old-school, nasty, cytotoxic, cell-killing drugs, but there is not much in the way of targeted therapies for pancreatic cancer—at least, not anything that’s worked,” Martin said. A BAG3-targeting treatment could be a game changer in a cancer that is often a death sentence, but Martin warned that there is a long way to go to show that its antibodies work in people. Intrepida plans to bring its first antibody into the clinic in 2021.
“We’re already engaged in additional studies on efficacy and things like dose response, as well as CMC work necessary to make commercial antibodies,” Martin said.
The San Diego-based biotech has a few ideas of where else this technology can go, but it’s keeping them under wraps for now until it’s put them through the paces.
And when Martin and Laurent are ready to go hunting again for their next big thing? They’ll want to return to Europe.
“Europe in general, but Italy in particular, doesn’t have the same range of connections to pharma and their researchers don’t have an immediate go-to VC fund,” Martin said.
“It was very heartening to see this superb research coming out of a university that doesn’t really register on U.S. investors’ minds very much … There are some real diamonds in the rough in Europe and I think if we in the future were to go and look for more things, we would spend a lot more time there,” he said.