Scientists are trying to advance cancer immunotherapy by developing new ways of getting T cells to target tumors. Some this research still involves removing a patient’s T cells and engineering them, then infusing those cells back into the patient. Marengo Therapeutics is developing drugs that coax immune cells into action without removing or engineering a single one. On Monday, it unveiled its approach along with $80 million and a lead program being prepared for human testing next year.
Margeno’s drugs are antibodies. Many antibody drugs are already available that turn on the immune system to fight cancer, but this response can go beyond the cancer and spark potentially dangerous side effects. Cambridge, Massachusetts-based Marengo is developing antibodies that bind to T cell receptors (TCRs), which are found on the surface of T cells. More specifically, Marengo’s drugs target V beta TCR variants.
Zhen Su, the startup’s CEO, said that binding to this target can selectively activate potent T cells that will provide the desired response to a patient’s cancer. Furthermore, Marengo’s drugs are not focused on just a single tumor antigen. The company’s drugs are intended to target many antigens, generating a broader response.
“You can target four or five [tumor antigens],” said Su, who joined Marengo from Merck KGaA, where he was senior vice president and head of global oncology. “Down the road, when the tumor escapes, [T cells are] fit to tackle that tumor.”
Marengo calls its technology selective T cell activation repertoire, or STAR. The company’s approach is new biology that represents new understanding of how to activate T cells, Su said. Marengo has been working with the lab of Adrian Hayday, a professor of immunobiology at King’s College London. Su said he expects Hayday’s research will be published in coming months.
Marengo has been incubating within venture capital firm Apple Tree Partners for the past two years. Andrew Bayliffe, the startup’s chief scientific officer and a venture partner at Apple Tree, said there are not any therapeutic antibodies that directly go to TCRs, bind to them, and activate T cells. He added that targeting V beta TCR variants can activate a larger population of T cells, but not the entire population of these immune cells. There are 30 or so of these variants. Targeting certain ones can activate the ones that will offer the best response to a patient’s tumors.
Other biotechs developing cancer immunotherapies that target TCRs include TScan Therapeutics and TCR2 Therapeutics. Those companies work with T cells collected from the patient. Adaptimmune Therapeutics is developing off-the-shelf TCR therapies made from induced pluripotent stem cells. Adaptimmune’s progress drew the interest of Roche, which committed $300 million to the biotech in September to begin a five-year alliance developing TCR therapies.
Lead Marengo drug candidate is code-named STAR0602. The antibody fusion molecule is designed to bind to and activates a specific V beta TCR variant T cell subset. The company said that the drug also delivers signals to that same T cell to enhance its anti-tumor activity. The company plans to advance that drug into clinical testing in 2022 for advanced and metastatic solid tumors. Su said that the new capital will be used to support that program, as well as to build a library of antibodies to build out the company’s pipeline.
Marengo’s potential advantage goes beyond selectively activating T cells to fight tumors, Su said. The company’s antibodies also activate memory T cells that stand ready to respond to the cancer if it returns. The company’s approach may also offer better safety and tolerability. Maregno’s antibodies don’t release pro-inflammatory signaling proteins to the extent of other T cell therapies. The company’s research incorporates insights from Elstar Therapeutics, a separate Apple Tree company that launched three years ago. Bayliffe said that Elstar, which is no longer active, was an antibody company while Marengo is an immunology company.
Marengo is building a library of antibodies. The company plans to add additional programs that engage other types of immune cells, potentially going beyond cancer to address areas such as infectious disease and autoimmune disorders.
“That’s why we believe this is a fundamental discovery that is so unique,” Bayliffe said. “We’re only at the beginning so we’re super excited.”
Photo by Marengo Therapeutics