InteliSpark client WntRx has been awarded a National Institutes of Health (NIH) Phase I Small Business Technology Transfer (STTR) grant worth $225,000 funded by the National Cancer Institute. The grant is for the STTR project, "Investigation of Antibody-Drug Conjugates of a Novel Target." This will enable WntRx to compete for a NIH Phase II STTR award.
WntRx Pharmaceuticals Inc. is building on the promise of Wnt signaling by applying its unique capabilities to discover and develop non-toxic, selective drugs for the treatment of patients with critical unmet medical needs. The company focuses on the development of novel, safe, selective, oncogenic specific inhibitors of Wnt signaling active in the treatment of cancer.
Antibody–drug conjugates (ADCs) are monoclonal antibodies (mAbs) that are covalently linked to cell-killing drugs and have emerged as a major modality in anti-cancer treatment. As antibody engineering and linker-payload optimization are becoming mature, the discovery and development of new ADCs is increasingly dependent on the identification and validation of new targets that are suitable to this approach.
LGR4 (leucine-rich repeat containing, G protein-coupled receptor 4) is a seven transmembrane domain receptor that is highly upregulated expression in the majority of solid tumors, including colorectal, lung, and ovarian cancers. LGR4 functions as a receptor of the R-spondin group of stem cell factors to potentiate Wnt signaling.
WntRX has generated and characterized a panel of highly potent and specific mAbs against native LGR4. Preliminary data showed that LGR4 mAbs conjugated with a potent cytotoxin were able to inhibit the growth of several cancer cell lines with high LGR4 expression in vitro and tumor xenografts in vivo. Here we propose to determine the potency, efficacy, and therapeutic window of anti-LGR4 ADCs in xenograft models of patient-derived tumors to establish proof-of-principle for the use of LGR4-targeded ADCs for the treatment of LGR4-high tumors. These results and conclusions may, for the first time, validate LGR4 as a novel target for the development of ADC-based therapeutics that has the potential to treat a large population of cancer patients.