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Telik Reports Preclinical Results at AACR Annual Meeting

PALO ALTO, Calif., April 28 /PRNewswire-FirstCall/ -- Telik, Inc. (Nasdaq: TELK) announced results of studies on two of its drug development programs that were presented at the 100th annual meeting of the American Association for Cancer Research (AACR) in Denver, CO. The abstracts can be found on the Telik website,

In vivo Characterization and Mechanism of Action of Orally Active Aurora Kinase/ VEGFR Inhibitors; Abstract # 1764

Aurora kinases are Ser/Thr kinases that play an important role in chromosome alignment, segregation and cytokinesis during mitosis. Over-expression of Aurora kinases has been demonstrated in both solid tumors and leukemia and is considered to be associated with aneuploidy and carcinogenesis. Inhibition of Aurora kinase activity induces growth arrest and apoptosis in cells and leads to tumor-growth inhibition in xenograft models of human cancer.

Key findings:

  • Telik researchers presented additional data for a novel class of small molecule drug candidates showing strong and equipotent inhibition of Aurora kinase and VEGFR kinase, with IC50s less than 10 nM.
  • These compounds induced growth arrest, polyploidy and apoptosis in human cancer cell lines, such as HCT116 (colon), HL60 (promyelocytic leukemia) and A549 (lung) - reflecting cell lines with intact or defective p53-dependent post-mitotic checkpoints.
  • More than 80% inhibition of tumor growth was seen in an HL60 xenograft model following a once daily oral dosing schedule.
  • Drug inhibition of aurora kinase and VEGFR activity in tumor samples of treated animals was established by analysis of markers, such as histone H3 phosphorylation and CD31.

Anti-Tumor Efficacy and Molecular Mechanism of TLK58747; Abstract # 4515

Telik researchers identified a novel alkylating agent, TLK58747, which functions as a prodrug, without the need for enzymatic processing, and which does not release an activation byproduct known to be associated with toxicity of other alkylating agents (acrolein).

Key findings:

  • TLK58747 inhibited the growth of nine established cell lines of various tumor types and retained its effectiveness against cancer cell lines resistant to standard cancer chemotherapeutics including adriamycin, paclitaxel, and carboplatin.
  • Treatment of human cancer cells with TLK58747 led to the activation of the DNA damage-response pathway, and produced G2/M cell cycle arrest in human solid tumor cell lines. The resulting apoptosis or senescence of these cells may depend on their p53 status.
  • In vivo, TLK58747 demonstrated significant antitumor activity both orally and parenterally against a wide variety of human tumor types, including breast, pancreatic, prostate, and colorectal carcinomas, as well as glioma and promyelocytic leukemia.

Telik, Inc. of Palo Alto, CA, is a clinical stage drug development company focused on discovering and developing small molecule drugs to treat cancer and inflammatory diseases. The company's most advanced investigational drug candidates in clinical development are TELINTRA(R), a modified glutathione analog for the treatment of cytopenias due to myelodysplastic syndrome or chemotherapy, and TELCYTA(R), a tumor-activated prodrug for the treatment of advanced ovarian cancer and non-small cell lung cancer. Telik's product candidates were discovered using its proprietary drug discovery technology, TRAP(R), which enables the rapid and efficient discovery of small molecule drug candidates.

TELIK, the Telik logo, TELINTRA, TELCYTA and TRAP are trademarks or registered trademarks of Telik, Inc.

SOURCE Telik, Inc.
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