The immune system can’t fight disease if its cells don’t reach their targets. In some cancers and rare immune deficiency disorders, immune cell levels are too low. X4 Pharmaceuticals has developed drugs that it says can help restore these counts to normal, and the company now has $27 million to test them in key clinical trials.
Cambridge, MA-based X4 has two lead candidates, one an immuno-oncology drug for solid tumors, and a second for WHIM syndrome, a rare immunodeficiency disorder. CEO Paula Ragan (pictured above) says the funding will power a Phase 3 study in WHIM that could support a filing for FDA approval, if successful.
In cancer, X4 is pushing its lead drug X4P-001-IO into a 45-patient Phase 2 study for kidney cancer. A Phase 1b study in melanoma is ongoing. Ragan says the new cash will carry the company far enough to report data from the cancer studies and the Phase 3 WHIM study, which should start in the second half of next year.
X4’s drugs are taken as pills. They target CXC chemokine receptor type 4 (CXCR4), a receptor that plays a role in the movement of immune cells. Tumors can suppress cancer-fighting immune cells. Ragan says X4P-001-IO blocks the CXCR4 receptor, which has the effect of mobilizing cancer-fighting T cells from the bone marrow. Restored to normal levels, the T cells can find the cancer cells and destroy them.
In its Phase 1b kidney cancer study, one patient out of the 14 who enrolled showed a complete response to treatment. In the ongoing melanoma study, patients are treated with the X4 drug then with a checkpoint inhibitor, which works by blocking a protein that tumors use to evade the immune system. Ragan says the X4 drug could take these “cold tumors” and make them “hot,” or recognizable to checkpoint drugs.
The CXCR4 receptor is also X4’s target for rare, chronic diseases known as primary immunodeficiency diseases because the immune system malfunctions. When the CXCR4 receptor is the culprit, it leads to lower-than-normal levels of immune cells. X4’s X4P-001-RD is a lower-dose form of its cancer drug. Ragan says that by blocking the malfunctioning receptor, X4P-001-RD helps restore immune cell levels closer to those of a healthy person. That’s what the company reported for a Phase 2 study in WHIM. Ragan says this approach to the disease could be called an immunotherapy.
“That is a term more comfortably used in oncology, but I think at this point it could be used in rare disease,” she says.
X4 launched in 2015 led by Ragan, whose experience includes six years at Genzyme. The company now employs a number of former Genzyme employees. Ragan says former Genzyme CEO Henri Termeer, who died in May, mentored her after she left the company. He led the seed investment in X4, and continued to counsel Ragan as she grew her new company.
X4’s Series B round attracted new investors but was led by the same group of investors from the company’s $37.5 million Series A round two years ago. All remain undisclosed except for Cormorant Asset Management, which is the largest investor, Ragan says.
Photo by X4 Pharmaceuticals.