Mersana Therapeutics Presents Data Demonstrating XMT-1001 Substantially Accumulates in Tumor and Results in Significantly Prolonged Drug Exposure
Preclinical pharmacokinetic data presented at AACR 101st Annual Meeting 2010-
CAMBRIDGE, Mass., April 20 /PRNewswire/ -- 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.
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
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
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
The poster was presented on Tuesday, April 20, 2010, from 9:00
AM to 12:00 PM.
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.
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
Web Site: http://www.mersana.com/
Posted: April 2010