STA-9584
Vascular Disrupting Agent

Program Overview

About STA-9584

Within tumors, the growth of thousands of tumor cells requires the support of single, fragile blood vessels that, like tumor cells, rapidly proliferate.

Drugs that target tumor vessels (tumor vasculature) could therefore starve tumor cells of oxygen and nutrients, leading to the rapid death of these cells, including tumor cells resistant to other therapies.

Synta has completed lead optimization of a small-molecule vascular disrupting agent that is designed to rapidly destroy existing tumor vasculature. This vascular disrupting approach contrasts with anti-angiogenic approaches that inhibit the growth of new tumor vasculature through protracted drug administration. Tests in tumor models have demonstrated the robust, rapid efficacy of this vascular disrupting agent against both chemotherapy-sensitive and -resistant tumors, as well as a promising safety profile.

Mechanism of Action

STA-9584 is among a class of compounds known as Vascular Disrupting Agents, or VDAs. In preclinical models, we have observed that STA-9584 efficiently kills both cancer cells in tumors, as well as the endothelial cells that form blood vessels in tumors, without affecting the vasculature of non-tumor tissues. Because STA-9584 appears to be highly potent and possess a mechanism that is different from many other classes of anti-cancer agents, we believe that STA-9584 has the potential to be used in both single-agent and combination settings in the clinic.

We believe that the inhibition of angiogenesis and disruption of existing tumor vasculature is a compelling therapeutic approach, as it has the potential to effectively prevent transport of oxygen and essential nutrients needed by the tumor and may lead to tumor shrinkage, and possibly, complete tumor eradication. First generation angiogenesis inhibitors, such as Avastin, work primarily by preventing the formation of new tumor vessels. In contrast, STA-9584's anti-vasculature effects are two-fold: disrupting both new and established tumor vessels. We believe that STA-9584's more complete anti-vasculature mechanism, in combination with an independent ability to directly kill cancer cells, may increase the potential anti-cancer activity of this compound versus first generation angiogenesis inhibitors and other endothelial cell-targeted agents.

Clinical Trials

STA-9584 is in preclinical development at this time.

Presentations

References for Vascular Disrupting

• Nature Reviews Cancer, 2005, 5: 423-435: Disrupting tumor blood vessels.

• Clinical Cancer Research, 2004, 10: 415-427: Vascular targeting agents as cancer therapeutics.