On October 16, 2019 Navire Pharma, Inc., a BridgeBio Pharma, Inc. subsidiary developing small molecule inhibitors of the protein tyrosine phosphatase SHP2 (Src homology 2 domain-containing phosphatase), reported preclinical data demonstrating the potential for the Company’s SHP2 inhibitor to lung cancer tumor cells that have acquired resistance to EGFR inhibitors, which are common targeted cancer medicines (Press release, Navire Pharma, OCT 16, 2019, View Source [SID1234542303]). The data will be presented at AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) on October 29, 2019.
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"Our work with MD Anderson’s Institute for Applied Cancer Science (IACS) adds to the growing body of evidence that SHP2 is an important node in MAPK signaling and supports combining a SHP2 inhibitor with an RTK inhibitor in RTK-driven cancers," said Shafique Virani, CEO of Navire Pharma. "The aim of BridgeBio’s BBP-398 program is to rapidly translate this exciting science into the clinic to evaluate the program’s potential to manage treatment-resistant cancers. We are preparing the program to be ready for clinical testing in 2020."
In a poster entitled "Discovery of IACS-13909, an allosteric SHP2 inhibitor that overcomes multiple mechanisms underlying osimertinib resistance," Yuting Sun, Ph.D., a member of the Institute for Applied Cancer Science at MD Anderson Cancer Center, from which Navire licensed its SHP2 inhibitors, will present preclinical data demonstrating that the allosteric SHP2 inhibitors were able to reduce growth of EGFR-driven non-small cell lung cancer (NSCLC) in vitro and in vivo. Importantly, IACS-13909 enhanced the anti-tumor activity of osimertinib, a front-line therapy for EGFR mutated NSCLC, when used in combination with osimertinib in preclinical models.
SHP2, a conserved protein tyrosine phosphatase, is a critical node in growth factor, cytokine and integrin signaling, all of which are important in the progression of cancer. SHP2 regulates multiple downstream signaling pathways including RTK/MAPK and the adaptive immune response through checkpoint inhibition. Alterations in RTK/MAPK and checkpoint inhibition pathways are common in cancer. Thus, targeting SHP2 may offer a potential new approach to treat this disease.