Checkpoint inhibitors do one thing: release the molecular brake that keeps immune cells from recognizing and targeting tumors. This cancer immunotherapy approach has saved countless lives and turned drugs from Merck and Bristol Myers Squibb into blockbuster products.
But what if a single drug could block checkpoint proteins while simultaneously sparking an anti-tumor response? That’s what Shattuck Labs aims to do. Its lead asset is in development under a partnership with Takeda Pharmaceutical (NYSE: TAK), and now the biotech has $118 million more to advance additional compounds to human testing. The Series B round of financing announced this week was led by Redmile Group.
Shattuck first disclosed raising money in 2018, a $46.6 million round that was completed with little fanfare and few details about the company’s plans. Other than the deal with Takeda—which revealed no financial information—the biotech has mostly maintained radio silence. Things are different now.
From operations in Research Triangle Park, NC, and Austin, TX, Shattuck is developing drugs intended to offer a multi-pronged approach to cancer, CEO Taylor Schreiber says. In addition to blocking checkpoint proteins the way that Merck (NYSE: MRK) drug pembrolizumab (Keytruda) does, Shattuck aims to stimulate the tumor necrosis factor (TNF) superfamily, proteins that play a role in immune response. The goal of this dual approach is to address cancers that don’t respond to checkpoint inhibition alone. But achieving both functions in a single drug has been difficult to do with antibodies.
Shattuck’s drugs are fusion proteins. Schreiber says his company designs its drugs using proprietary technology called Agonist Redirected Checkpoint (ARC). The drugs it produces have six costimulatory domains, which are the parts of the drug that activate an immune response.
“These drugs have a structure that can match a target in a way that antibodies never can,” Schreiber says.
Shattuck’s most advanced program, SL-279252, is currently in Phase 1 testing under a partnership with Takeda that began in 2017. In addition to blocking PD1 checkpoint proteins, the drug stimulates OX40, a member of the TNF receptor superfamily. In preclinical studies, Shattuck reports that this combination enhanced the proliferation of T cells and the increased the production of signaling molecules that play a role in the immune response to cancer. This dual approach offers a way to overcome a tumor’s mechanism for suppressing the immune system, Schreiber says.
The most advanced internal Shattuck program, SL-172154, is a fusion protein that blocks CD47 and also stimulates CD40. The former is a protein on the surface of tumors that sends out a “don’t eat me” signal to macrophages, a type of immune cell. By blocking this protein, CD47 drugs are intended to clear the way for macrophages to gobble up tumors. That’s how the cancer treatments developed by Menlo Park, CA-based Forty Seven (NASDAQ: FTSV) work. Early clinical trial results from that biotech’s lead drug were so encouraging that Gilead Sciences (NASDAQ: GILD) shelled out $4.9 billion to buy the company.
But Schreiber says it’s not enough to just get macrophages to eat tumor cells. These cells also need to display bits of the gobbled-up tumors so the immune system recognizes and responds to them—and another way to trigger that immune response is by stimulating CD40. Shattuck’s CD47/CD40 drug is being readied for clinical testing.