Mersana Therapeutics Announces Poster Presentations Demonstrating Differentiating Aspects of ADC Platform Technology at the American Association for Cancer Research Annual Meeting 2018
Poster Title: Unique pharmacologic properties of Dolaflexin-based ADCs – a controlled bystander effect
Session: Antibody-Drug Conjugates: Agents and Technologies
Session Date and Time: April 15, 2018, 1:00 –
Location: McCormick Place South, Exhibit Hall A, Poster Section 35
Poster Board Number: 754/21
Poster Title: Synergy of an anti-HER2
Session: Late-Breaking Research: Immunology 2
Session Date and Time: Tuesday Apr 17, 2018
Location: McCormick Place South, Exhibit Hall A, Poster Section 44
Poster Board Number: LB 294/16
XMT-1522 is a Dolaflexin ADC targeting HER2-expressing tumors. XMT-1522 comprises a novel, proprietary HER2 antibody which is conjugated with Mersana’s Dolaflexin platform – a Fleximer polymer linked with a proprietary auristatin payload. XMT-1522 provides a drug load of approximately 12 molecules per antibody, specifically designed to improve potency while simultaneously increasing tolerability. XMT-1522 has the potential to extend HER2-targeted therapy beyond the current “HER2-positive” populations into patients with lower levels of HER2 expression. The Phase 1 protocol will evaluate XMT-1522 in patients with advanced HER2-positive breast and gastric cancer, as well as advanced breast cancer with low HER2 expression and non-small cell lung cancer. Mersana received
The Dolaflexin platform is designed to increase the efficacy, safety and tolerability of ADCs by overcoming key limitations of existing technologies based on direct conjugation of a payload molecule to an antibody. Dolaflexin consists of Fleximer, a biodegradable, highly biocompatible, water soluble polymer, to which are attached multiple molecules of our proprietary auristatin drug payload, using a linker specifically optimized for use with our polymer. The high-water solubility of the Fleximer polymer compensates for the low solubility of the payload, surrounding the payload and protecting it from aggregation and maintaining stability in circulation. Multiple molecules of this Dolaflexin polymer-drug conjugate can then be attached to an antibody of choice, which significantly increases the payload capacity of the resulting ADC. This approach differs from most other ADC technologies where the payload is directly conjugated to the antibody via a linker. Using its Dolaflexin platform, Mersana has been able to generate ADCs with Drug-to-Antibody Ratio (DAR) between 12 to 15 while maintaining acceptable pharmacokinetics and drug-like properties in animal models. This represents a three to four-fold increase in DAR relative to traditional ADC approaches.
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Source: Mersana Therapeutics, Inc.