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Update data from preclinical studies with XMT-1536, an antibody-drug conjugates or ADC being developed by Mersana Therapeutics targeting NaPi2b, were presented in a poster at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications, held  October 26 – 30, 2017 in the Pennsylvania Convention Center in Philadelphia, Pennsylvania.  was given by Rebecca Mosher, M.D., Executive Director, Translational Medicine, Mersana Therapeutics.[1]

The data confirms that XMT-1536 may offer positive results for patients with ovarian cancer, which ranks, according to the American Cancer Society, fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. A woman’s risk of getting ovarian cancer during her lifetime is about 1 in 75. Overall, a woman’s lifetime chance of dying from ovarian cancer is about 1 in 100.

The American Cancer Society estimates that in the United States in 2017 about 22,440 women will receive a new diagnosis of ovarian cancer. About 14,080 women will die from ovarian cancer.

MabPlex
 

This means that ovarian cancer represents a major unmet medical need.

Anti-sodium-dependent phosphate transport protein
XMT-1536 is a highly potent anti-sodium-dependent phosphate transport protein (NaPi2b; SLC34A2) immunoconjugate comprised of an average of 10-15 DolaLock payload molecules conjugated to XMT-1535, a proprietary humanized anti-NaPi2b antibody, via the Dolaflexin ADC platform. NaPi2b is an antigen highly expressed in the majority of non-squamous NSCLC and epithelial ovarian cancer. XMT-1536 is scheduled to begin Phase I clinical trials in early 2018.


…the data … support … NaPi2b [as an] outstanding target for ADC development … and the Dolaflexin ADC platform allows us to fully exploit the advantages of this … target…


Outstanding target
“The data presented at AACR-NCI-EORTC further support that NaPi2b is an outstanding target for ADC development and that the Dolaflexin ADC platform allows us to fully exploit the advantages of this interesting target,” said Donald Bergstrom, M.D., Ph.D, Chief Medical Officer, Mersana Therapeutics.

“These results in ovarian cancer models are consistent with data we’ve previously presented on the broad activity of XMT-1536 in preclinical models of non-squamous non-small cell lung cancer (NSCLC). We look forward to initiating Phase I testing of XMT-1536 in patients with ovarian cancer, non-squamous NSCLC and other NaPi2b-expressing tumors by early 2018,” he added.

The study revealed that XMT-1536 induced at least a 50% median reduction in tumor volume relative to baseline in 10/19 (53%) primary patient-derived ovarian cancer xenograft models, that were selected for testing without prior knowledge of NaPi2b expression status. The activity of XMT-1536 was comparable in models derived from tumors from treatment-naïve patients as well as models that came from patients with heavily pre-treated tumors.

Target expression
When NaPi2b target expression was evaluated using a proprietary immunohistochemistry (IHC) assay discovered at Mersana in conjunction with XMT-1536, there was an association between NaPi2b IHC H-score and tumor volume change after XMT-1536 treatment. Among tumors with an H-score ≥70, 10/12 (83%) of models achieved 50% or greater reduction in tumor volume after XMT-1536 treatment, vs. 0/7 (0%) models with an H-score ‹70. Applying the same IHC assay to primary human ovarian tumors, 12/20 (60%) tested tumors had an H-score ≥70, indicating the majority of human ovarian tumors express levels of NaPi2b associated with deep regressions in response to XMT-1536 in pre-clinical models.

“We are extremely pleased with the results of this research and the progress the program has made to date,” said Rebecca Mosher, M.D., Executive Director, Translational Medicine, Mersana Therapeutics.

“The data described in the presentation suggest that XMT-1536 could be broadly active in ovarian cancer, and that we may have a diagnostic tool that could further enrich the patient population to enhance clinical benefit,” she further noted.