On October 7, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that XMT-2056, its first Immunosynthen STING-agonist ADC candidate, targets a novel epitope of human epidermal growth factor receptor 2 (HER2) and presented new preclinical data during a plenary session at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Triple Meeting) (Press release, Mersana Therapeutics, OCT 7, 2021, View Source [SID1234590939]).

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"Previously, across multiple targets and models, we demonstrated that our Immunosynthen ADCs can stimulate the innate immune system in a targeted manner in both tumor cells and tumor-resident myeloid cells – a "one-two punch" resulting in robust efficacy. New head-to-head preclinical data comparing XMT-2056 to TLR7/8-agonist ADC and systemically-administered STING agonist benchmarks further supports the potential advantages of XMT-2056 to offer greater efficacy and a wider therapeutic index," said Timothy B. Lowinger, PhD, Chief Science and Technology Officer of Mersana Therapeutics. "In addition, new data with XMT-2056 in combination with trastuzumab supports our rationale for selecting an antibody that recognizes a novel epitope of HER2, providing broad combination potential with approved and investigational HER2 therapies."

"STING is a fundamental mechanism yet approaches to date have been unsuccessful at stimulating the innate immune system in a targeted manner. Our Immunosynthen platform not only has the potential to address this limitation but also is designed to allow us to extend our ADC development efforts beyond cytotoxic payloads, which we believe represents a significant advancement in the ADC field," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "We are particularly excited about the potential of XMT-2056 to offer a novel approach to the treatment of HER2-expressing tumors both as a single agent and in combination."

Previously reported preclinical data suggest that XMT-2056 offers a highly differentiated approach, enabling tumor-targeted delivery of a STING agonist with improved efficacy and tolerability over a systemically-administered STING agonist benchmark. In vitro and in vivo studies demonstrate that STING-agonist ADCs activate the STING pathway in both tumor-resident immune cells and tumor cells, offering the potential for an increased therapeutic index and an advantage over other innate immune activating pathways.

The Company has evaluated Immunosynthen ADCs across a wide range of antibodies, targets, tumor models and mouse strains and observed broad efficacy and consistent results demonstrating target-dependent anti-tumor effects and has selected HER2 as the first target for clinical evaluation with XMT-2056. The Company developed a differentiated anti-HER2 antibody that binds a novel epitope distinct from that of trastuzumab and pertuzumab, providing the opportunity for combinations with these well-established anti-HER2 therapies.

New preclinical data presented today at the Triple Meeting include:

XMT-2056 demonstrated increased efficacy in both high and low HER2 SCID mouse models in comparison to benchmark agents such as a trastuzumab-TLR7/8 agonist ADC as well as a small molecule systemically-administered STING agonist.
XMT-2056 showed excellent in vivo efficacy as a single agent in a SKOV3 HER2 high model and this efficacy is further enhanced by combining XMT-2056 with a 3 mg/kg dose of trastuzumab.
XMT-2056 was generally well-tolerated in NHP studies with no clinical signs and no adverse findings in clinical pathology or histopathology after single and repeat IV doses of 9 mg/kg, at exposures far exceeding those necessary for efficacy in mouse models, indicating the potential for a wide therapeutic index.