XMT-1107 is a novel, first-in-class anti-angiogenic with broad potential across multiple oncology indications. Mersana designed XMT-1107 to maximize the dramatic anti-angiogenic activity of the fumagillin class, as demonstrated in clinical trials with the fumagillin analog TNP-470, but also to overcome pharmacokinetic limitations, including an extremely short half-life, as well as reversible CNS toxicity that prevented further clinical development of fumagillins despite their clinical promise. XMT-1107 has demonstrated dramatically improved pharmacokinetics and no evidence of CNS toxicity, establishing it as a potential new anti-angiogenic drug with significant therapeutic advantages.
XMT-1107 is a novel conjugate of a proprietary fumagillin analog, Fleximer® polymer backbone and a customized linker that was specifically designed to prevent delivery of the active moiety to the brain to avoid CNS-related side effects. The Fleximer polymer protects the drug in the systemic circulation, providing dramatic improvements in pharmacokinetics. The drug works by inhibiting the target MetAP2, and has anti-angiogenic properties, cutting off essential blood supply to tumors, as well as potential direct anti-tumor effects.
A Phase 1 clinical trial evaluating XMT-1107 has been completed in refractory advanced solid tumors. The drug candidate is partnered with Teva for all indications worldwide, except for Japan, through a deal signed in April 2010. Japanese sales of the two top-selling angiogenesis inhibitors, Avastin® and Nexavar®, are expected to reach in excess of $1 billion per year.1
Numerous preclinical studies of XMT-1107 have demonstrated potent anti-angiogenic effects with associated tumor growth inhibition and significantly enhanced survival. Additional laboratory studies have demonstrated its superior anti-cancer activity compared to other anti-angiogenics, synergistic activity in combination with other anti-cancer agents, a favorable safety profile and an extended half-life. Additional preclinical data presented at AACR 2010 showed that XMT-1107 exhibits enhanced biodistribution and sustained plasma exposure.
XMT-1107 is partnered with Teva for all oncology indications worldwide, except for Japan. Mersana is open to discussions with parties interested in licensing Japanese rights.