FDA Grants XMT-2056 an Orphan Drug Designation

Orphan drug designation has been granted by the FDA to XMT-2056 for the treatment of patients with gastric cancers.

The FDA granted an orphan drug designation to XMT-2056, an immunosynthen STING-agonist antibody-drug conjugate (ADC), for the treatment of patients with gastric cancers, according to Mersana Therapeutics.1

XMT-2056 revealed more than 100-fold increased potency compared to the free STING-agonist payload. Using mice, XMT-2056 displayed robust anti-tumor immune activity, showing only minimal increases in systemic cytokine levels, and the treatment exhibited significant benefit over the benchmark free STING-agonist payload.

Within vitro and in vivo studies, XMT-2056 was shown to be able to activate the STING pathway in both tumor-resident immune cells and tumor cells, offering a potential advantage over other innate immune activating pathways. Investigators discovered XMT-2056 was well-tolerated in non-human primates at significantly higher exposure levels than those required for anti-tumor activity, and the ADC presented favorable pharmacokinetics after repeat doses.2

Gastric cancer accounts for approximately 1.5% of all new cancers diagnosed in the United States each year, according to the American Cancer Society.

“The FDA’s decision to grant orphan drug designation to XMT-2056 for the treatment of gastric cancer is an important recognition of its potential in this area of high unmet medical need,” said Anna Protopapas, president, and chief executive officer of Mersana Therapeutics in the press release. “We are eager to bring XMT-2056 and its unique mechanism of action into the clinic mid-year to investigate its safety, tolerability and anti-tumor activity in gastric and other cancers.”

The company designed XMT-2056 to offer a differentiated and complementary therapeutic approach to existing and emerging solid tumor treatments. Mersana Therapeutics developed XMT-2056, leveraging a differentiated antibody that binds to a novel HER2 epitope, which provides the opportunity for treatment as a monotherapy and in combination with other agents, including other anti-HER2 therapies.

The company aims to initiate a phase 1 trial of XMT-2056 in a range of HER2 expressing tumors, such as breast, gastric and non–small-cell lung cancers, during 2022.

Mersana has previously developed and are in the process of testing other ADC’s such as, upifitamab rilsodotin (UpRi), a Dolaflexin ADC targeting NaPi2b that is being studied in UPLIFT (NCT03319628),3 a single-arm registrational trial in patients with platinum-resistant ovarian cancer, as well as in UPGRADE (NCT04907968),4 a phase 1/2 umbrella trial evaluating upifitamab rilsodotin in combination with other ovarian cancer therapies. Mersana has another early-stage program: XMT-1660, a Dolasynthen ADC targeting B7-H4.

Mersana therapeutics announces fda grant of orphan drug designation to XMT-2056 for the treatment of gastric cancer. Press release. GlobeNewswire; May 19, 2022. Accessed May 23, 2022. https://bit.ly/38Ol1em
Duvall JR, Bukhalid RA, Cetinbas NM, et al. XMT-2056, a well-tolerated, immunosynthen-based STING-agonist antibody-drug conjugate which induces anti-tumor immune activity. Cancer Res. 2021;81(suppl 13):1738. doi:10.1158/1538-7445.AM2021-1738
First-in-human study of XMT-1536 in cancers likely to express NaPi2b. ClinicalTrials.gov. Updated April 8, 2022. Accessed May 23, 2022. https://clinicaltrials.gov/ct2/show/NCT03319628?term=NCT03319628&draw=2&rank=1
Study of upifitamab rilsodotin in combination with other agent(s) in participants with high-grade serous ovarian cancer (UPGRADE). ClinicalTrials.gov. Updated April 13, 2022. Accessed May 23, 2022. https://clinicaltrials.gov/ct2/show/NCT04907968?term=UPGRADE%2C+upifitamab+rilsodotin&draw=2&rank=1
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