PTC Therapeutics has announced that its oncology program targeting BMI1, a protein linked to drug-resistant cancers, has entered a phase I study in patients with advanced solid tumors. The open-label, first-in-human study will investigate the safety and pharmacokinetics of PTC596, an orally available small molecule. PTC's BMI1 program is supported by a collaboration with the Wellcome Trust.

BMI1 has been implicated in a wide variety of cancers and has been demonstrated to contribute to therapeutic resistance and treatment failure. BMI1 is thought to play a role in the survival and maintenance of tumor stem cells in many cancers, including central nervous system cancers such as glioblastoma. Elevated levels of BMI1 have been associated with advanced tumor grade and a poor prognosis.

"We're excited to begin clinical trials for PTC596, an investigational drug that targets an important stem cell regulator, BMI1, which is elevated in a wide array of tumor types," said Robert Spiegel, M.D., chief medical officer, PTC Therapeutics. "In preclinical models, PTC596 reduced BMI levels leading to depletion of the cancer stem cell population. Importantly, we saw this effect when PTC596 was used alone and in combination with current standards of care."

"Targeting cancer stem cells by BMI1 inhibition is a promising approach to address the challenge of drug-resistant cancers," said Lillian Siu, M.D., Princess Margaret Cancer Center, professor of oncology, University of Toronto. "Cancer is a complex problem and the development of treatments that focus on molecular targets shows promise for the next generation of cancer therapies to make a difference in patients' lives."

PTC's collaboration with the Wellcome Trust began in June 2010 when the Wellcome Trust awarded PTC $5.4 million to support the development of drugs that target BMI1.