Abstract 2124: A potent therapeutic antibody BGM-2121 targeting parathyroid hormone-related peptide (PTHrP) for pancreatic cancer

Abstract Although approximately 35% of approved drugs target G-protein-coupled receptors (GPCRs), cancer-specific GPCR-targeted therapies remain limited. Notably, several GPCRs and their ligands, including parathyroid hormone-related protein (PTHrP), are overexpressed in various solid tumors, including pancreatic cancer. In about 30% of pancreatic cancer cases, the PTHLH gene is co-amplified with the KRAS oncogene on chromosome 12, a phenomenon also observed in lung and colorectal cancers. Furthermore, the PTHLH gene can drive cancer progression through self-amplification. To address this, BioGate has developed BGM-2121, a potent humanized IgG1 monoclonal antibody targeting the N-terminal region (a.a. 1-34) of PTHrP, aiming to treat pancreatic cancer by targeting the PTHrP/PTH1R pathway. Preclinical studies have confirmed the specificity and antitumor activity of BGM-2121. In vitro assays demonstrated the antibody's high affinity and specificity for PTHrP, while in vivo animal studies using human pancreatic cancer cell models in mice showed significant antitumor activity. Notably, BGM-2121 effectively reduced tumor growth, halted disease progression in mouse models, and significantly extended survival. Additionally, in lung squamous cell carcinoma models, BGM-2121 successfully prevented and even reversed hypercalcemia and weight loss—key contributors to humoral hypercalcemia of malignancy (HHM) and cancer cachexia in human patients. Comprehensive safety and pharmacokinetic (PK) studies, including toxicokinetics (TK) and GLP-compliant repeated-dose toxicity studies, have thoroughly evaluated the safety profile of BGM-2121. In conclusion, this potent PTHrP-targeting antibody shows considerable promise as a therapeutic agent for cancers with PTHrP overexpression (e.g., pancreatic and lung cancers), humoral hypercalcemia of malignancy, and PTHrP-mediated cancer cachexia. We are currently preparing to submit an Investigational New Drug (IND) application to the TFDA and plan to initiate clinical trials to evaluate its potential as a novel biologic treatment for hard-to-treat metastatic cancers in Taiwan. Citation Format: Chiawen Ho, Chi-Feng Tseng, Chong-Jen Huang. A potent therapeutic antibody BGM-2121 targeting parathyroid hormone-related peptide (PTHrP) for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2124.