Date: 2015-04-28
Type of information: Initiation of preclinical development
phase:
Announcement:
Company: PTC Therapeutics (USA - NJ)
Product: PTC596 - oncology program targeting BMI1
Action
mechanism: PTC596 is an orally active small molecule that targets tumor stem cell populations by reducing the function, activity and amount of BMI1. PTC596 acts by altering and destroying the BMI1 protein through a process called phosphorylation. PTC596 has potently inhibited BMI1 function in multiple tumor cell lines. In in vitro tests, PTC596 has preferentially targeted chemotherapy resistant cancer stem cells. Specifically, PTC596 preferentially depleted cancer stem cells in assays with tumor cell lines from fibrosarcoma, prostate and colon cancers. Conversely, the cytotoxic chemotherapies carboplatin, temozolomide, methotrexate and indibulin enriched the population of cancer stem cells in this assay. In animal cancer models using human tumors, weekly oral dosing of PTC596 provided tumor control, including reduction of tumor size. PTC596 and the commonly used chemotherapy paclitaxel were both effective at controlling tumor growth in these animal models. However, PTC596, but not paclitaxel, decreased BMI1 levels, indicating a reduction in cancer stem cells. Consistent with this reduction in BMI1 levels, after transplanting tumor cells from one animal to another, the resulting tumors treated with PTC596 had lower levels of cancer stem cells than either untreated tumors or tumors treated with paclitaxel.
Disease: advanced solid tumors
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 28, 2015, PTC Therapeutics announced that its oncology program targeting BMI1, a protein linked to drug-resistant cancers, has entered a Phase 1 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. 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.
