On June 22, 2020 RGENIX, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported it is presenting an abstract on RGX-019, RGENIX’s pre-clinical antibody program in development (Press release, Rgenix, JUN 22, 2020, View Source [SID1234561348]). RGENIX’s abstract, "In Vivo Safety and Efficacy of RGX-019, a MerTK Targeting Monoclonal Antibody" was accepted for the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which this year was scheduled as two virtual meetings. The abstract results will be presented as a virtual poster presentation (LB-090) during the Late-Breaking Research: Immunology 1 session on June 22, by RGENIX’s Vice President of Research Dr. Isabel Kurth, who is senior author on the abstract.
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MerTK is a member of the TAM family of receptor tyrosine kinases and is predominantly expressed on macrophages as well as on cancer cells from a number of solid and hematologic malignancies. The binding of ligands to MerTK on cancer cells activates signaling that increases proliferation, angiogenesis, and drug resistance. On immune-suppressive M2 macrophages, MerTK signaling promotes immune tolerance. Therefore, there is rationale to target MerTK both to suppress tumor growth and activate anti-tumor immunity.
RGX-019 is a novel humanized MerTK targeting monoclonal antibody with a unique mechanism of action. As outlined in the presentation, RGX-019 was found to bind with high affinity to human and monkey MerTK, without detectable binding to related TAM receptors AXL or Tyro. RGX-019’s unique mechanism drives MerTK degradation through receptor internalization and lysosomal trafficking, resulting in the elimination of MerTK from the surface of treated cells. In vitro, RGX-019 inhibited human cancer cell viability and induced immune-stimulatory cytokine expression in M2 macrophages, consistent with robust inhibition of MerTK signaling. RGX-019 treatment in vivo led to near complete elimination of MerTK from the surface of tumor cells, which was associated with anti-tumor efficacy in mouse xenograft models.
Importantly, RGX-019 demonstrated a favorable safety profile in a 28-day dose-range finding toxicology study in monkeys. Of note, retinal toxicity – a finding associated with other MerTK targeting approaches – was not observed at any dose of RGX-019. The results overall demonstrate that RGX-019 can potently target MerTK signaling on both cancer cells and immune-suppressive M2 macrophages with a novel mechanism, resulting in anti-tumor activity with a wide therapeutic window.
Masoud Tavazoie, M.D., Ph.D., and Chief Executive Officer of RGENIX, said, "The results presented today demonstrate the potential for RGX-019 to be a best-in-class MerTK inhibitor. Its unique characteristics have yielded a favorable safety and efficacy profile in animals that provides a solid foundation for further development of RGX-019. We are excited to move RGX-019 through further IND-enabling studies and ultimately into clinical development."