Updating, 6/8/10 blog, Positive Data from Telomerase Inhibitor Clinical Trial of Imetelstat (GRN163L) …
This enzyme is expressed in a wide range of malignant tumors, and its activity is essential for the indefinite replicative capacity of cancer that enables malignant cell growth.
- Imetelstat is a lipidated short chain oligonucleotide that binds with high affinity and specificity to the catalytic site of telomerase, resulting in competitive inhibition of enzyme activity;
- Telomerase is absent or expressed only transiently at low levels in most normal adult tissues;
- Proprietary manufacturing chemistry and the addition of a 5’ lipid chain have enabled the molecule to penetrate cells and tissues throughout the body;
- Telomerase has now also been shown to be a target for cancer stem cells.
Imetelstat has demonstrated anti-tumor effects in a wide range of preclinical xenograft models of human solid and hematological tumors, and potent activity against cancer stem cells derived from primary patient samples or cancer cell lines from multiple tumor types.
- Imetelstat has been tested in 6 GERN sponsored Phase 1 clinical trials at 22 US medical centers treating over 180 patients examining the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug, alone or in combination with other standard therapies in patients with different hematological and solid tumors;
- A randomized Phase 2 clinical trial of imetelstat has been initiated in non-small cell lung cancer;
- A 2nd randomized Phase 2 trial is planned in breast cancer and 2 single arm Phase 2 clinical trials are planned in multiple myeloma and essential thrombocythemia.
Preclinical studies have also demonstrated that imetelstat can inhibit clonogenic growth of both primary patient samples and subpopulations from cell lines enriched for cancer stem cells from multiple tumor types.
- These subpopulations show resistance to several conventional chemotherapeutic agents. Cancer stem cells capable of clonogenic growth may play an important role in the rapid re-growth of tumors after initial reduction by standard treatments.