Forty Seven

Fierce 15

Looking to up the ante on immune response to cancer and realize the early promise of anti-CD47 therapy

CEO: Jonathan MacQuitty
Based: Menlo Park, CA
Founded: 2016
Clinical focus: Early trials for its anti-CD47 antibody Hu5F9-G4 against a host of cancers

The scoop: Coming out of Irv Weissman’s Stanford lab, Forty Seven is targeting CD47, a protein that scrambles a key immune response that helps guard tumors against a process called phagocytosis, in which the cancer cells are devoured by a phagocyte. Back in 2012, data from Stanford on its early work raised eyebrows, and now its spinoff company is working on a new way of spurring an immune response to cancer.

What makes Forty Seven Fierce: Over the past 5 years, a lot of work in oncology has been focused on harnessing the immune system to attack tumors, with companies like Merck, Bristol-Myers Squibb and Roche all now marketing PD-1/PD-L1 checkpoint inhibitors that do exactly that. These drugs have gained many headlines and produced some strong data--in certain patient populations--and has meant that most Big Pharma firms, and even smaller biotechs, would be remiss not to have an I/O candidate in their pipeline.

Forty Seven, however, is not looking to follow the crowd and work on a checkpoint inhibitor, but rather wants to create a next-gen form of immuno-oncology using its anti-CD47 compound. MacQuitty explains: “All of the I/O work to date has been with the adaptive immune system [which is made up of systemic cells and processes that eliminate or prevent pathogen growth], but we have in parallel the innate immune system, and that’s modulated by a white blood cell called a macrophage.

“You can think of these as kind of like Pac-Man: They go around the body and eat up foreign cells, literally engulfing and digesting them. But many cancers have learned to upregulate a certain signal on their surface, and that’s what CD47 is. It essentially uses a 'don’t eat me' signal to the macrophage, so it can go about growing and spreading without being engulfed.”

MacQuitty says that what the original Stanford team has pioneered over the last 8 years is to understand the biology of CD47 and then develop an antibody which finds it and masks it, so that the tumor is no longer hiding from the innate immune system. Then, the Pac-Man-esque macrophages can come along and eat the tumor cells.

“There is an enormous pool of published, really exciting preclinical data on this, and now we’re working two clinical studies using this agent: One in a liquid tumor in acute myeloid leukemia and one in a [undisclosed] solid tumor, and we now have 25 patients that have been treated. Initially of course with a new agent like this we have to use a relatively low dose to ensure there are no safety issues. But we now know that not only is the agent safe, but its tolerability is very good as well, and we’re not seeing the kinds of side effects that have been seen with checkpoint inhibitors in terms of skin sensitivity or GI problems.”

He says that they are now getting plasma concentration levels which are the same as seen in preclinical work, which MacQuitty says were very strong, and is therefore showing an early translation into the clinic.

But MacQuitty admits that it’s not “an easy agent to use,” as the protein they go after is also seen on red blood cells, notably older red blood cells, so the biotech has had to develop some “interesting dosing regimens” to combat this. “But we’re confident we have got this right; we published our work on this at ASCO this year, so I think what we’ve got on our hands is a very powerful agent that can be used as well in conjunction with lots of other treatments, from chemotherapy to checkpoint inhibitors, so it’s very exciting.”

The biotech raised $75 million in its Series A at the start of the year, with help from Google’s venture arm GV. Google is “doing a lot more than just the money,” but MacQuitty says that just what this is can’t be made public right now.

Investors: GV (formerly Google Ventures), Lightspeed Venture Partners, Sutter Hill Ventures and Clarus Ventures

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Forty Seven