Mersana Therapeutics, a platform-based cancer therapeutics company, announced today that a review of the Company's lead compound, XMT-1001, will appear in the November 12, 2009 special issue of Advanced Drug Delivery Reviews on Polymer Therapeutics: Clinical Applications and Challenges for Development. The review article, entitled, "XMT-1001, a novel polymeric camptothecin pro-drug in clinical development for patients with advanced cancer," was authored by Alexander V. Yurkovetskiy, Ph.D., and Robert J. Fram, M.D., both of Mersana, and provided an overview of XMT-1001 in the context of other topoisomerase I inhibitors conjugated to polymers or encapsulated in liposomes.
XMT-1001 is a conjugate of the broad-spectrum cytotoxic camptothecin (CPT) that employs Mersana's Fleximer® platform. XMT-1001 is currently in a Phase 1 trial in patients with advanced solid tumors. Non-Fleximer-linked CPT was shown to be active in prior clinical studies conducted by the National Cancer Institute (NCI), but was discontinued due to severe bladder toxicity. The XMT-1001 program significantly improves on the clinically active drug, providing broad-spectrum activity with potentially better efficacy and safety.
According to the review, XMT-1001 demonstrated an improved therapeutic window compared to CPT or irinotecan in human tumor xenograft studies. The review also reports that XMT-1001, unlike many other conjugated CPT analogs, provides a slow and sustained systemic release of well defined drug products, enabling drug delivery to tumor, both in low molecular weight and in macromolecular forms. This dual-release mechanism of XMT-1001 may result in lower levels of CPT in the urine and less bladder toxicity, a serious dose-limiting toxicity associated with CPT and CPT conjugated to other polymers.
Preliminary data from the ongoing Phase 1 trial of XMT-1001 support these findings, revealing favorable pharmacokinetics, safety, and potential for therapeutic activity, demonstrated by multiple heavily pre-treated patients with advanced cancer exhibiting prolonged stable disease at non-myelosuppressive doses of XMT-1001. To date, XMT-1001 has not caused severe diarrhea or hemorrhagic cystitis, serious side effects associated with non-linked CPT or irinotecan.
"This review article once again demonstrates the unique advantages of linking Fleximer to cancer compounds. Specifically, Mersana's development of a CPT-conjugated drug with a dual-release mechanism could potentially address both the bladder and gastrointestinal toxicities that have previously been a concern with these drugs, while also potentially enhancing efficacy," said Julie Olson, Ph.D., CEO of Mersana. "Mersana has made solid progress over the last year, as XMT-1001 moves through Phase 1 and we prepare to advance our second candidate, XMT-1107, into the clinic. We're encouraged by the attention our Fleximer® technology is garnering for its ability to be chemically linked to small molecules and biologics such as siRNA and peptide therapeutics to transform existing and experimental anti-cancer agents into new, patentable drugs with superior pharmaceutical properties. We look forward to continuing to advance existing and new compounds in the coming year."
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