On April 5, 2022 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 it will present three posters highlighting data for XMT-1660, XMT-2056, and the Immunosynthen ADC platform at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 to be held in New Orleans, Louisiana from April 8-13, 2022 (Press release, Mersana Therapeutics, APR 5, 2022, View Source [SID1234611463]).
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"ADC innovation is at the core of Mersana’s strategy, and we have made significant progress in building out an innovative pipeline of potential cancer medicines. Our preclinical data show the potential of XMT-1660 in a range of B7-H4 expressing tumors and the power of our Dolasynthen platform," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "The preclinical profile of XMT-2056 as monotherapy and in combination with standard of care therapies in both HER2-high and HER2-low expressing models reinforces the differentiation of the Immunosynthen platform. We look forward to advancing both molecules into the clinic in mid-2022."
XMT-1660 is a Dolasynthen ADC targeting B7-H4, a target selectively expressed on tumors in areas of high unmet medical need, including breast, endometrial, ovarian and other cancers. The data show that a single dose of XMT-1660 has anti-tumor activity in both triple-negative breast cancer (TNBC) and estrogen receptor (ER)-positive breast cancer xenograph models. Higher B7-H4 expression is associated with greater anti-tumor activity of XMT-1660 in preclinical studies. Mersana expects a Phase 1 clinical trial for XMT-1660 to start in mid-2022.
XMT-2056, Mersana’s first Immunosynthen STING-agonist ADC, targets a novel epitope of HER2, and is designed to offer a differentiated and complementary therapeutic approach to the treatment of HER2-expressing tumors. The preclinical data presented show that XMT-2056 demonstrates robust anti-tumor activity as a monotherapy in both HER2-high and HER2-low expressing models. XMT-2056’s complementary mechanism of action results in increased efficacy in combination with trastuzumab, pertuzumab, anti-PD-1, or trastuzumab deruxtecan in preclinical studies. Mersana expects to initiate a Phase 1 clinical trial of XMT-2056 in mid-2022.
Immunosynthen is Mersana’s immunostimulatory ADC platform designed to take ADCs beyond traditional cytotoxic drugs to targeted stimulation of the innate immune system. Data show that anti-tumor activity of Immunosynthen STING-agonist ADCs involves the targeted activation of the STING pathway in an antigen binding-dependent manner in both tumor-resident immune cells and in tumor cells. In addition to delivery to the tumor cell via antigen binding and internalization, data from multiple models demonstrate Fcγ-R1 is the major receptor that mediates delivery to a specific population of myeloid cells resident in primary human tumors, eliciting potent anti-tumor responses in preclinical studies.
Details of the presentations are as follows:
Poster Title: Anti-tumor effect of XMT-1660, a B7-H4 targeting antibody drug conjugate, in an unselected panel of patient derived xenograft models of breast cancer
Poster Board Number: 8
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody Drug Conjugates
Date/Time: Monday, April 11, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 21
Poster Title: XMT-2056, a HER2-targeted Immunosynthen STING-agonist antibody-drug conjugate, binds a novel epitope of HER2 and shows increased anti-tumor activity in combination with trastuzumab and pertuzumab
Poster Board Number: 5
Session Category: Immunology
Session Title: Immunomodulatory Agents and Interventions 2
Date/Time: Tuesday, April 12, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 37
Poster Title: Tumor cell-targeted STING-agonist antibody-drug conjugates achieve potential anti-tumor activity by delivering STING agonist specifically to tumor cells and FcγRI-expressing subset of myeloid cells
Poster Board Number: 15
Session Category: Immunology
Session Title: Innate Immunity to Cancer
Date/Time: Monday, April 11, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 40