Mersana Therapeutics, a platform-based cancer therapeutics company, announced positive preclinical pharmacokinetic data for its lead development candidate, XMT-1001, which is currently in a Phase 1 clinical trial in patients with advanced solid tumors. The results were presented in a poster session at the AACR 101st Annual Meeting 2010 in Washington, DC, held April 17-21, 2010. XMT-1001 is a conjugate of the anti-cancer molecule camptothecin (CPT) that employs Mersana’s Fleximer platform. Data from the study demonstrated that XMT-1001 substantially accumulates in tumors and tissue and provides significantly prolonged exposure to the conjugate drug and its release products, including highly potent CPT, providing potential efficacy and safety advantages.
XMT-1001 was designed to produce a prolonged exposure in the plasma and tumor and to improve the safety margin of CPT. The conjugate’s dual-release mechanism, which occurs via intermediates CPT-SI and CPT-SA, provides a slow and sustained release of CPT. In the current study, the researchers evaluated the plasma, tumor and tissue pharmacokinetics of XMT-1001, CPT-SI, CPT-SA and CPT in a preclinical model of human colon cancer.
Results from the study demonstrate that conjugating the active drug CPT to Fleximer resulted in substantial tumor accumulation and that the duration of tumor exposure to XMT-1001 extended for at least 14 days after a single dose. This significantly prolonged presence of XMT-1001 and its release products in the tumor may explain XMT-1001’s improved therapeutic index relative to CPT in nonclinical studies.
William Zamboni, Pharm. D., Ph.D., Associate Professor at the University of North Carolina and lead author of the study, commented: “XMT-1001’s improved tumor distribution and extended localized release of the small molecule prodrugs and potent CPT are consistent with the improved safety and efficacy over existing drugs of the same class. In addition, the prolonged presence of XMT-1001 in the tumor is one of the longest tumor exposures currently reported after a single intravenous dose.”
“The results of this study further support the existing nonclinical data for XMT-1001, which have shown that the conjugated drug significantly improves upon CPT and other competitive agents, demonstrating broad-spectrum activity with potentially better efficacy and safety,” said Julie Olson, Ph.D., President and CEO of Mersana. “Additionally, results from our ongoing Phase 1 trial of XMT-1001 have shown its favorable tolerability, pharmacokinetics, and also anti-tumor activity in patients with refractory tumors.”
Date: April 20, 2010
Source: Mersana Therapeutics
Filed Under: Drug Discovery