Abstract 5294: MDX-124, a novel annexin-A1 antibody, induces significant anti-cancer activity in multiple preclinical models

Abstract

Abstract Annexin-A1 (ANXA1) is secreted from both cancer and immune cells in response to several physiological stimuli and modulates cellular functions through interactions with formyl peptide receptors (FPR1/2). Overexpression of ANXA1 has been observed in multiple cancers, including triple-negative breast (TNBC), colorectal, lung, pancreatic, gastric and prostate, and correlates with poor prognosis and decreased overall survival. ANXA1 has also been shown to promote cancer cell proliferation, angiogenesis, migration and drug resistance, and to modulate the tumor microenvironment. MDX-124 is a novel humanized antibody targeting ANXA1. Previously we presented data demonstrating its significant anti-proliferative activity. Here we provide further data on the mechanism of action of MDX-124, notably its impact on tumor growth, cell cycle arrest and migration in several preclinical cancer models. Incubation of pancreatic (BxPC-3), lung (A549) and TNBC (MDA-MB-231) cancer cell lines with MDX-124 for 24 h decreased the proportion of cells in S-phase by up to 18.3% with a concomitant increase in G1 phase of up to 33.5% versus untreated cells. This effect occurred in a dose-dependent manner and is consistent with an MDX-124 mediated increase in cell cycle arrest. After 72 h incubation with MDX-124, the migratory ability of gastric (AGS), prostate (PC-3), TNBC (MDA-MB-231), lung (A549), pancreatic (MIA PaCa-2) and colorectal (LoVo) cancer cells was significantly reduced in a dose-dependent manner when compared to untreated controls. Proteomic analysis following incubation of MDX-124 with a panel of cancer cell lines for 72 h demonstrated substantial alterations in the level of expression and phosphorylation of multiple key oncogenic proteins. In the MycCaP-Bo syngeneic model of bone metastatic prostate cancer, mice treated with the murine analog of MDX-124 (10 mg/kg, BIW) had a 52% reduction in mean tumor growth after 14 days compared to isotype control treated mice. In conclusion, our data indicate that targeting ANXA1 with MDX-124 inhibits key tumorigenic processes in several clinically challenging cancer indications. MDX-124 therefore provides an innovative approach to cancer therapy. Medannex initiated a First-In-Human study in Q4 2021 to evaluate MDX-124 in solid malignancies known to overexpress ANXA1. Citation Format: Fiona C. Dempsey, Hussein Al-Ali, Scott J. Crichton, Charlene Fabian, Chris Pepper, Bin-Zhi Qian, Xue-Feng Li, Christopher N. Parris. MDX-124, a novel annexin-A1 antibody, induces significant anti-cancer activity in multiple preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5294.