The Double Agent Drug

February 17, 2016
By: Angela Spivey, DCI Development

Ines Batinic-Haberle and colleagues developed BMX-001 based on a discovery in a Duke basic research lab. The drug will first be tested in patients with brain cancer and head and neck cancer in clinical trials at Duke in 2016.Duke Cancer Institute member Ines Batinic-Haberle, PhD, holds a vial of liquid up to the light, revealing its red hue. This liquid is the product of 25 years of her work. In a few weeks, it will be injected into human cancer patients for the first time.

The hope: during treatment with radiation, the compound will reduce damage to normal tissue while helping kill the cancer. That’s what the drug, named BMX-001, did in years of studies in mice and other animals with brain cancer and head and neck cancer.

Batinic-Haberle, professor of radiation oncology, created BMX-001 to mimic an enzyme that the body naturally produces to protect cells from everyday wear and tear.

The business of living—breathing, metabolism—creates byproducts that, over time, can damage cells. The body defends itself against this “oxidative stress” by many means. One of those is an enzyme called superoxide dismutase (SOD), which Duke scientist Irwin Fridovich discovered along with his then doctoral student Joe McCord, in the late 1960s.

In animal studies, the drug acts like a "double agent"--it protects normal cells from radiation while promoting the death of cancer cells. The red color comes from porphyrin--a compound that helps make up the blood protein hemoglobin. Photos by Jim Rogalski.

In animal studies, the drug acts like a “double agent”–it protects normal cells from radiation while promoting the death of cancer cells. The red color comes from porphyrin–a compound that helps make up the blood protein hemoglobin. Photos by Jim Rogalski.Batinic-Haberle worked with Fridovich for more than a decade and developed BMX-001 to mimic the SOD enzyme. The synthetic version gets inside cells more efficiently and accumulates there. “My major contribution was figuring out a structure for the synthetic compound to efficiently mimic the SOD enzyme,” she says.

The drug seems to act like a double agent--it protects normal cells but promotes death of cancer cells. After studying the drug for years, Batinic-Haberle, Mark Dewhirst, DVM, PhD, and colleagues found that once it gets inside normal cells, BMX-001 activates natural anti-oxidant defenses.

A striking image of BMX-001 along with species involved in its actions. Photo: Artak Tovmasyan, PhD.But in cancer cells, those defenses are disrupted, and high levels of toxic oxidants are already circulating. In those cells, BMX-001 promotes the production of toxins, setting off programmed cell death—a type of planned “suicide.”

In February 2016, BMX-001 will be tested in a phase 1/2 clinical trial at Duke in patients with late-stage glioma (a large class of brain tumors). Katy Peters, MD, PhD, will lead the trial at Duke Cancer Center, testing the safety of the drug and whether it improves response to treatment. The researchers hope that the drug will also reduce neurocognitive damage from radiation.

Later in 2016, Duke will launch a second trial, in patients with head and neck cancer, led by David Brizel, MD. The scientists hope that the drug will reduce common side effects from radiation, such as damage to the salivary glands, dry mouth, and trouble swallowing.

A company called BioMimetix JVLLC licensed BMX-001 from Duke and is sponsoring these trials along with the National Institutes of Health. For more information about the glioma trial, visit clinicaltrials.gov.

3-D animation (below) courtesy of Artak Tovmasyan, PhD., an investigator involved in the development of BMX-001.