CAMBRIDGE, Mass., April 20 Mersana Therapeutics, a platform-based cancer therapeutics company, announced today 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.
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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.
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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."
Poster Information
Abstract number 3696 was authored by: Mark D. Walsh, Suzan K. Hanna, and Jeremy Huynh, of UNC Eshelman School of Pharmacy; John D. Benson, Carolina B. Cabral, Alex Yurkovetskiy, Robert J. Fram and Timothy B. Lowinger, of Mersana Therapeutics; and William C. Zamboni, of UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, UNC Institute of Pharmacogenomics and Individualized Therapy, and Carolina Center for Cancer Nanotechnology Excellence.
The poster was presented on Tuesday, April 20, 2010, from 9:00 AM to 12:00 PM.
About XMT-1001
XMT-1001 is a conjugate of Fleximer and camptothecin (CPT), a broad-spectrum cytotoxic that inhibits the enzyme topoisomerase I, causing DNA damage to cancer cells. In prior Phase 2 trials (not sponsored by Mersana), the free drug CPT demonstrated evidence of anti-tumor activity, but also exhibited safety concerns, including severe bladder toxicity. Nonclinical studies of XMT-1001 in oncology models have shown significant improvement over the clinically active CPT and irinotecan, evidenced by broad-spectrum activity with better efficacy and safety.
About Fleximer®
Fleximer is a novel, biodegradable and bio-inert polymer that can be chemically linked to small molecules, biologics and nucleic acids to enhance their pharmacokinetic and safety profiles. Fleximer has been proven to transform existing and experimental agents into new, patentable drugs with superior properties. The Fleximer platform has broad and versatile applications across therapeutic categories and enhances the delivery of small molecule, protein and nucleic acid-based therapeutics.
About Mersana Therapeutics, Inc.
Mersana Therapeutics employs its biodegradable polymer platform (Fleximer®) to create new and better medicines. We are advancing our own clinical-stage pipeline of novel compounds with the potential to address multiple oncology indications. The company has also developed a proprietary Fleximer-based siRNA delivery system that is currently in preclinical studies. Mersana Therapeutics has operations in Cambridge, MA and London, England. For more information, visit www.mersana.com.
Fleximer® is a trademark of Mersana Therapeutics, Inc.
SOURCE Mersana Therapeutics
