MENLO PARK, Calif., April 8, 2013 /PRNewswire/ -- Preclinical data showing high potency, excellent pharmacokinetics and single-agent anti-cancer activity of NT-113, a novel irreversible Pan-ErbB Tyrosine Kinase Inhibitor under development by NewGen Therapeutics, was presented in a poster session today at the American Association of Cancer Research Meeting in Washington, D.C.
Data showed that NT-113 is a very potent inhibitor of ErbB subtypes, including EGFR, HER2 and ErbB4, in a panel of over 100 tyrosine kinases and is highly active against erlotinib (Tarceva®) and gefitinib (Iressa®) resistant cancer cells with EGFR mutations including T790M, L858R, and d-746-750. Potent anti-cancer activity was demonstrated in T790M mutant non-small cell lung (NSCLC) cancer and HER2 positive gastric cancer xenograft models. Pharmacokinetic data showed excellent oral bioavailability, a long half-life and the ability to penetrate the blood barrier at therapeutic concentrations.
In collaboration with C. David James, Ph.D., University of California, San Francisco (UCSF), NT-113 was studied for both in vitro and in vivo for activity in glioblastoma (GBM). NT-113 showed a broad spectrum of in vitro activity across multiple human GBM cell lines. In addition, data showed statistically significant anti-cancer activity and increase in survival relative to a control group in an intracranial GBM39 mouse xenograft model. GBM39 is a human GBM cell line that carries the disease driving EGFRvIII mutation.Key differentiating features of NT-113 include:
- Equipotency across EGFR, HER2 and ErbB4
- Excellent distribution of NT-113 into the brain at therapeutic doses (4:1 brain/plasma concentrations)
- Excellent oral bioavailability and pharmacokinetics
- Potency against the distinct EGFR mutations found in both GBM and other solid tumors including extra-cranial malignancies such as NSCLC, breast cancer and melanoma
- Demonstrated potent anti-cancer activity in an HER2 positive gastric cancer, T790M mutant NSCLC and GBM39 intracranial mouse xenograft studies