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Home > Press > Mersana's Second Development Candidate, XMT-1107, Shows Superior Pharmacokinetics and Anti-Tumor Activity in Studies Presented at American Association of Cancer Research Meeting

Abstract:
- Data Show Fleximer(R) Extends Exposure to Conjugated Drug -

Mersana's Second Development Candidate, XMT-1107, Shows Superior Pharmacokinetics and Anti-Tumor Activity in Studies Presented at American Association of Cancer Research Meeting

Cambridge, MA | Posted on April 20th, 2009

Mersana, a platform-based cancer therapeutics company, today announced positive results of preclinical studies for its second development candidate, XMT-1107, in two posters at the 2009 Annual Meeting of the American Association of Cancer Research (AACR) in Denver.

The studies showed that XMT-1107, a novel anti-angiogenic fumagillin analog conjugated to Mersana's proprietary Fleximer(R), demonstrated superior anti-tumor activity in tumor xenograft models in comparison to other anti-angiogenic agents and extended exposure to the conjugated drug, supporting the potential clinical utility of XMT-1107 as an anti-cancer agent. Full text of the abstracts can be viewed online at the AACR website at www.AACR.org.

"We're encouraged by the ongoing progress we're seeing with XMT-1107, which targets a novel mechanism to inhibit endothelial cell proliferation and has the potential to target a wide variety of angiogenic tumors," said Julie Olson, Mersana CEO. "Earlier drugs in this class showed promising activity in the clinic but were discontinued due to reversible neurological toxicity. Conjugation of our novel fumagillin 'warhead' to Fleximer using a specific linker technology reduces CNS exposure in animal models to below detection limits. We look forward to advancing XMT-1107 into clinical studies by early 2010."

"Anti-angiogenic and anti-tumor activity of XMT-1107, a fumagillin-derived polymer conjugate, and its in vivo release product XMT-1191"

By Laura C. Akullian, Cheri A. Stevenson, John Benson, Robert J. Fram, Timothy B. Lowinger

This study showed that XMT-1107 has enhanced anti-angiogenic and anti-tumor activity compared to small molecule analogs delivered without the benefit of Fleximer. XMT-1107 inhibited human MetAP2 in vitro, was highly active in human umbilical vein endothelial cell (HUVEC) proliferation assays, and showed anti-angiogenesis activity in vivo in the Matrigel plug assay. Additionally, XMT-1107 was active in a number of syngeneic and xenograft tumor models. The enhanced antiangiogenic and in vivo anti-tumor activity of XMT-1107 compared to its in vivo release product XMT-1191 clearly demonstrated the benefit of conjugating XMT-1191 to Fleximer(R) and supports the potential clinical utility of XMT-1107 as an anti-cancer agent.

"Pharmacokinetics of a novel fumagillol conjugate XMT-1107 in the rat"

By Alex Yurkovetskiy, Dana L. Shkolny, Laura C. Akullian, Mao Yin, Laraine L. Meyers, Robert J. Fram, Timothy B. Lowinger.

This study evaluated the pharmacokinetics (PK) of XMT-1107 and its conjugate release product, XMT-1191, in rats. The XMT-1107 conjugate extended exposure to its corresponding drug release product, XMT-1191, while significantly reducing (> 500 fold) maximum XMT-1191 plasma levels (Cmax).

The data suggest that the slow rate of release of XMT-1191 from the polymer conjugate XMT-1107 provided a low but consistent exposure to the highly active XMT-1191 small molecule, providing an apparent half life of 22 hours compared with a half life of less than five minutes with free XMT-1191 administration. The data are consistent with the significantly higher in vivo activity seen for XMT-1107 relative to XMT-1191 in xenograft activity reported in a separate poster.

####

About Mersana Therapeutics, Inc.
Mersana, a privately held, venture backed company, utilizes its proprietary technology platform to transform existing and experimental anti-cancer agents into new, patentable drugs with superior pharmaceutical properties. Mersana's lead compound, XMT-1001, is currently in Phase I trials in cancer patients. Mersana's second compound, XMT-1107, is expected to move into the clinic by early 2010. Mersana's preclinical pipeline also includes proprietary targeting moieties employed with conjugates for delivery of siRNA and anti-cancer agents.

The key component of Mersana's platform is Fleximer(R), a novel, biodegradable and bio-inert polymer that can be chemically linked to small molecules and biologics. Fleximer(R) technology improves the therapeutic index of existing compounds by uniquely combining biodegradability with "biological stealth" properties, making Fleximer(R) materials and their conjugates long-circulating and non-immunotoxic. Fleximer(R) molecules are characterized by solubility in water, with stability in common manufacturing procedures. Mersana's investors include Fidelity Biosciences, ProQuest Investments, Rho Ventures, Harris & Harris Group and PureTech Ventures.

Fleximer and Mersana(R) are trademarks of Mersana Therapeutics, Inc.

For more information, please click here

Contacts:
Mersana Therapeutics, Inc.
840 Memorial Drive
Cambridge, MA 02139

Tel: 617.498.0020
Fax: 617.498.0109

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