Synta Pharmaceuticals' STA-9090 inhibits WT1 protein in AML

Feb 9 2010

Synta Pharmaceuticals Corp. (NASDAQ: SNTA) today announced that preclinical results presented at the “Bridging the Gap 2010” Hematologic Conference, held in Singapore City, Singapore, February 5-7, 2010, shows that STA-9090, a potent inhibitor of heat shock protein 90 (Hsp90), inhibits the Wilms’ tumor 1 (WT1) protein, a key transcription factor that drives disease progression in acute myeloid leukemia (AML) as well as certain other leukemias. STA-9090 is currently enrolling patients in two clinical trials in AML and other hematologic cancers.

“There is a very high need for new treatment options for patients with AML”

“There is no established therapy that durably inhibits WT1 oncogenic functions, which means there is a tremendous urgency to develop new therapeutic options for patients whose cancer is driven by this transcription factor,” said Swaminathan Padmanabhan, M.D., Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio. “In these studies, STA-9090 potently inhibited WT1 expression and demonstrated greater potency than the first generation Hsp90 inhibitor 17-AAG. Targeting WT1 expression by Hsp90 inhibitors such as STA-9090 may offer new strategies to limit the survival promoting effects of WT1 in myeloid leukemias including AML.”

In in vitro experiments, STA-9090 reduced the expression of WT1 in a dose-dependent manner in myeloid leukemic cells. In vivo results demonstrated inhibition of Hsp90 blocked tumor growth in a xenograft tumor model using leukemia cells expressing WT1. WT1 down-regulation by STA-9090 was also observed in primary myeloid leukemic blast cells isolated from AML patients.

“There is a very high need for new treatment options for patients with AML,” said Vojo Vukovic, M.D., Ph.D., Senior Vice President and Chief Medical Officer, Synta Pharmaceuticals. “The results presented today provide insight both into the underlying biology of what drives AML and into the potential role that STA-9090 could play in treating this disease. We are very encouraged with the ongoing clinical studies in hematologic malignancies, where STA-9090 has shown preliminary signs of clinical activity in patients and has been well tolerated to date.”