Chemical structure of XMT-1107
Mersana's XMT-1107 program is currently in preclinical development and is approaching Phase 1 clinical testing. XMT-1107 is a conjugate of Fleximer and a novel analog of fumagillin, an angiogenesis inhibitor with a mechanism of action distinct from agents that principally inhibit angiogenesis by targeting VEGF. Prior to Mersana's efforts, a small molecule fumagillin analog showed anti-cancer activity in several tumor types in Phase 1 and 2 trials, but development was discontinued because a short half-life required frequent intravenous dosing and reversible CNS toxicity was observed in patients. The XMT-1107 program provides key potential benefits over other analogs, including an extended half-life with sustained release of the active release product, as shown in nonclinical studies, as well as evidence of efficacy alone or in combination with other agents in human tumor xenograft models. Anti-angiogenic agents generated at least $4 billion in annual sales globally in 2007.
Mersana's Fleximer-linked drug, XMT-1107, provides key benefits over free fumagillin and other competitive agents, including:
- Extended half-life, resulting in a sustained plasma exposure, mimicking a prolonged, continuous infusion
- Improved solubility
- Anti-tumor activity in preclinical models alone or in combination is superior to other anti-angiogenic agents
- Preclinical studies show dramatic benefit of conjugated versus free small molecule at equivalent doses
- Preclinical activity in a wide variety of cancer models
- Patented release products due to novel conjugated small molecules
- Preclinical evidence for CNS safety and very low brain exposure in animals
- New mechanism-of-action will potentially drive adoption in rapidly growing multi-billion dollar drug class
