XMT-1001 is a novel cytotoxic drug conjugate from the established "tecan" drug class with proven broad activity across solid tumors. This next-generation topoisomerase 1 inhibitor is the first conjugate engineered using Mersana's proprietary conjugation system to enter the clinic.
Broadly active cytotoxic drugs are an important component of cancer treatment, but off-target toxicities and challenges with solubility and pharmacokinetics currently limit the clinical utility for approved topoisomerase 1 inhibitors. As a result, there exists a need for new, broadly active cytotoxics with improved toxicity and pharmacokinetic properties, and superior efficacy. Mersana designed XMT-1001 to be clearly differentiated within this class, and to distribute a novel, stabilized active topoisomerase inhibitor preferentially to tumors. Phase 1 and preclinical studies demonstrate that XMT-1001 results in significant improvements in pharmacokinetics, biodistribution, tolerability and efficacy, and is poised to capture the therapeutic potential for this drug class.
Mersana has also developed additional topoisomerase 1 inhibitor conjugates with novel release profiles. These preclinical-stage conjugates are supported by promising data that further validate Mersana's approach to developing next-generation topoisomerase 1 inhibitors.
XMT-1001 is a conjugate of a novel camptothecin analog, the Fleximer® polymer backbone and a customized linker, and was designed to produce a prolonged exposure to the tumor and to improve the safety and efficacy of the active drug payload. The drug works by inhibiting the topoisomerase 1 enzyme, thereby causing highly proliferating tumor cells to die.
The Fleximer polymer dramatically increases the solubility of the drug, extends its half-life and more effectively distributes stabilized drug to the tumor. The conjugate's dual-phase release mechanism, achieved via specific linker design, provides a slow and sustained release of the active drug, allowing significantly higher levels of drug to be dosed while minimizing off-target side-effects and providing the potential for greater efficacy. Mersana has also applied Fleximer and alternative linker technologies to its additional topoisomerase 1 inhibitor conjugates, achieving variations with similar beneficial properties.
XMT-1001 is being evaluated in an ongoing Phase 1b clinical trial in lung cancers, following successful completion of a Phase 1 clinical trial. Phase 2 clinical trials for XMT-1001 are planned to begin in 2012.
Lung cancer is one of the most common forms of cancer worldwide, but is not optimally addressed by currently available therapies. Estimates show that approximately $10.3 billion is spent each year on lung cancer treatment in the U.S. alone.1
Mersana's additional topoisomerase 1 inhibitor conjugates are preclinical-stage and have a strong supporting data package.
Mersana successfully completed a Phase 1 trial evaluating XMT-1001 in patients with advanced solid tumors. Results from this trial showed evidence of its potential clinical activity, with tumor shrinkage and prolonged stable disease in this heavily pre-treated patient population. XMT-1001 also demonstrated improved pharmacokinetics and a favorable safety profile free of the off-target toxicities observed with other drugs in its class, validating the improved biodistribution strategy achieved through Mersana's conjugation system.
In various preclinical studies utilizing cancer models, XMT-1001 exhibited evidence of anti-tumor activity superior to other drugs in its class, as well as improved survival. XMT-1001 has also shown significantly improved drug distribution and exposure to tumors compared to other drugs in its class. Additionally, preclinical data presented at AACR 2010 demonstrated that XMT-1001, by benefit of its polymer structure, substantially accumulates in tumors and provides significantly prolonged drug exposure.
Preclinical studies of Mersana's supporting pipeline of additional topoisomerase 1 inhibitor conjugates have shown that they are well tolerated and have potentially better efficacy than other drugs in the class.
Mersana currently holds worldwide rights to XMT-1001 and to its pipeline of additional topoisomerase 1 inhibitor conjugates, and is open to licensing discussions with interested parties.