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, today presented preclinical data for XMT-1592, its clinical stage Dolasynthen ADC targeting NaPi2b, as well as progress on its Immunosynthen STING-agonist ADC platform at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting.
“The advancement of XMT-1592 is another example of our commitment to innovation in the ADC field and to extending our leadership in NaPi2b-targeted therapy. The ongoing Phase 1 study aims to clinically validate the advantages represented by the preclinical data shown in the AACR poster,” said Timothy B. Lowinger, Ph.D., Chief Science and Technology Officer of Mersana Therapeutics. “With Immunosynthen, we are leveraging our expertise to extend the benefits of ADCs into the realm of immuno-oncology with the aim of stimulating the innate immune system in a targeted, safe and effective manner. These data demonstrate that across multiple targets, antibodies and pre-clinical models, the Immunosynthen STING-agonist ADC platform delivers robust, target-dependent anti-tumor effects at well-tolerated doses and induces tumor-specific immune memory and other hallmarks of immune activation. We remain on track to select our first Immunosynthen STING-agonist ADC development candidate in the second half of 2020.”
“We’ve made significant progress with our differentiated Dolasynthen and Immunosynthen ADC platforms to advance our pipeline,” said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. “These novel platforms, together with our clinically validated Dolaflexin platform, represent significant breakthroughs in the ADC field. Our vision is to continue to leverage these platforms to deliver meaningful therapies to patients in need.”
Details of the posters are as follows:
Poster Title: XMT-1592, a Site-Specific Dolasynthen-Based NaPi2b-Targeted Antibody-Drug Conjugate for the Treatment of Ovarian Cancer and Lung Adenocarcinoma
Poster Number: 2894
Date: June 22, 2020 at 9:00 a.m. ET and on demand
Session Type: Poster Session
XMT-1592 is an ADC created using Dolasynthen, Mersana’s proprietary, customizable and homogeneous platform designed to precisely optimize an ADC for a given target, drug-to-antibody ratio (DAR) and antibody. XMT-1592 is currently in an ongoing Phase 1 dose escalation study to determine the maximum tolerated dose (MTD) in patients with non-small cell lung cancer (NSCLC) adenocarcinoma and ovarian cancer. This poster evaluates the benefits of site-specific bioconjugation of Dolasynthen by reporting in vitro and in vivo comparisons of XMT-1592 to a stochastically conjugated version of the ADC. XMT-1592 shows improved in vivo activity, pharmacokinetics and clinical pathology relative to its stochastic counterpart. These data also show that XMT-1592 induced sustained tumor regressions in an NSCLC adenocarcinoma patient-derived xenograft.
Poster Title: Systemic Administration of STING-Agonist Antibody-Drug Conjugates Elicit Potent Anti-Tumor Immune Responses with Minimal Induction of Circulating Cytokines
Poster Number: 6706
Date: June 22, 2020 at 9:00 a.m. and on demand
Session Type: Poster Session
These data presented today show that Immunosynthen represents a novel STING-agonist ADC platform for the systemic administration of a therapeutic agent with targeted immune-stimulatory effects. These data show target-dependent anti-tumor immune responses in vitro and in vivo as a single well-tolerated dose for multiple targets in multiple preclinical models. The data also show that the STING-agonist ADC was more active (over 100-fold increased potency) with limited induction of systemic cytokines when compared to intravenously administered unconjugated (free) agonist, suggesting it may confer an improved therapeutic index. In addition, potent ADC-mediated tumor regression led to durable immunological memory in an immune competent model.