Mersana is advancing a robust pipeline of ADC therapies across multiple tumor types that have the potential to radically improve patients’ lives by increasing survival and quality of life.
XMT-1536: A first-in-class ADC targeting NaPi2b, a clinically validated ADC target
XMT-1536 is a Dolaflexin ADC targeting NaPi2b-expressing tumors. NaPi2b is an antigen highly expressed in 75 to 90% of both non-squamous NSCLC and epithelial ovarian cancer. NaPi2b was evaluated as an ADC (lifastuzumab vedotin) by Genentech, Inc., in studies that indicated that NaPi2b could be safely targeted by an ADC, with evidence of clinical activity in ovarian cancer. XMT-1536 is currently in Phase 1 clinical development in the dose escalation phase. It entered clinical development December 2017.
In our preclinical studies, XMT-1536 induced complete tumor regressions in an ovarian cancer model and an NSCLC adenocarcinoma model after three weekly doses of 3 mg/kg. In comparison, lifastuzumab vedotin failed to induce tumor regressions when similarly administered in three weekly doses of 3 mg/kg. XMT-1536 was also tested in eight patient-derived tumor models of NSCLC adenocarcinoma, where it led to complete or near-complete tumor regressions in five of eight models, and significant tumor growth delay in two of the remaining three models. These tumor regressions were durable at least 45 days post-dosing. Similarly, XMT-1536 was tested in fifteen ovarian patient-derived xenograft models where it led to complete or near complete tumor regressions in nine models and partial regressions in three models. Retrospective evaluation of NaPi2b expression appears to correlate with responses to XMT-1536. In an exploratory repeat dose non-human primate study of XMT-1536, no neutropenia was observed at payload doses that were at least four times the highest non-severely toxic dose of lifastuzumab vedotin and at least two times the dose that caused fatal neutropenia with lifastuzumab vedotin in non-human primates.1
 Lin et al, ClinCancer Res 2015, 21:5139-5150;
XMT-1522: A potent HER2-targeted ADC targeting patients not addressed by currently approved HER2 therapies
XMT-1522, is a Dolaflexin ADC targeting HER2-expressing tumors. On January 4, 2019 Mersana announced the discontinuation of the clinical development of XMT-1522 following a strategic evaluation of the program and the competitive environment.
Our vision is to leverage the power of our technologies to develop a leading ADC pipeline. We have multiple active programs at the discovery stage with the objective of bringing a new drug candidate forward into clinical development every twelve to twenty-four months.