Chemotherapy is like nuking the body with chemicals. It kills good and bad cells alike, which is why cancer patients undergoing treatment get fatigued and suffer through a whole host of side effects. A little startup built around research at the University of North Carolina called G1 Therapeutics thinks it’s got an answer to some of those ailments—a molecular shield, of sorts, that could help protect the body from the damage. Now it just has to amass the clinical data to prove it.
Sometime within the next few months, Chapel Hill, NC-based G1 will begin its first clinical trial for what’s called G1T28-1, a compound meant to help thwart some of the toxic effects of chemotherapy, like depletion of healthy red or white blood cells. It’ll mark the first clinical step in an ambitious journey for G1, a tiny, 10-person startup trying to make its drug candidate a mainstay in a slew of chemotherapy regimens. If G1 has its way, it’ll unseat big-selling biologic drugs like Amgen’s (NASDAQ: [[ticker:AMGN]]) darbepoetin alfa (Aranesp), which, despite safety issues that have reduced their use, are still administered to patients with chemotherapy-induced anemia.
“We would posit that this could potentially be standard of care for any patient getting chemo,” says CEO Mark Velleca, who began running G1 in May.
Of course, there’s a long road ahead before G1 can claim that’s a real possibility—G1T28-1 has got to deliver the goods in the clinic, beginning with that first study later this year.
G1 was formed around the work of Norman Sharpless, the associate director for translational research at UNC’s Lineberger Comprehensive Cancer Center; and Kwok-Kin Wong, an oncologist and researcher at Dana-Farber and Harvard. The two worked for years researching the steps cancer cells take to grow and divide, before homing in on two particular enzymes, cyclin-dependent kinases 4 and 6 (CDK4/6), that they thought to be important players in the process—particularly when it comes to cells in the bone marrow.
CDK4/6 are well-known targets. One of New York-based Pfizer’s (NYSE: [[ticker:PFE]]) most highly touted cancer drug prospects, palbociclib, binds to them, as do compounds from Eli Lilly (abemaciclib) and Novartis (LEE011). The enzymes have become hot targets for cancer drugs because, in some cases—like in estrogen-receptor positive breast cancer, for example—tumors depend on them to grow. Blocking the kinases, the reasoning goes, helps shrink such tumors.
Sharpless and Wong, however, thought to use CDK4/6 in a completely different way—to protect healthy cells from the toxic effects of chemotherapy and radiation. Chemo drugs and radiation work by killing cells that are in the process of dividing. Since cancer cells tend to divide more rapidly than healthy cells, they are preferentially affected by the treatments, but there is always some collateral damage to the normally dividing cells in the bone marrow, gut, and elsewhere. Sharpless and Wong theorized that if a drug could pause cell division in those healthy cells during cancer treatment, it would shield them—and therefore spare the patient from a host of side effects.
To do this, their idea was to administer a drug that could bind to CDK4/6—which turn out to be critical switches that allow cell division to proceed in bone marrow cells—just before chemotherapy or radiation is administered, to pause the normal cells’ division briefly. G1T28-1, for instance is designed to stick around “as long as the chemo is on board,” then “wash out,” Velleca says. In theory, this would prevent
