Rectify Pharma Presents Preclinical Data Supporting Development of Lead Candidate RTY-694 at The Liver Meeting® 2024
Rectify Pharmaceuticals, Inc., a biotechnology company developing positive functional modulators (PFMs), small molecule therapeutics that restore and enhance membrane protein function, today announced the presentation of in vitro and mouse model characterization data from its hepatobiliary program at the 75th Annual Liver Meeting® sponsored by American Association for the Study of Liver Diseases (AASLD), taking place in San Diego, CA, November 15 – 19, 2024.
In primary hepatocytes, RTY-694 directly and selectively increased both BSEP and ABCB4 protein levels and the cellular efflux of bile acids and phospholipids mediated by these ABC transporters. This mechanism is distinct from other small molecules that act at the mRNA level.
As a novel dual-acting BSEP and ABCB4 PFM, RTY-694 has the potential to provide benefit for a broad range of hepatobiliary diseases where dysregulated BSEP and ABCB4 activity leads to cholestasis and cholangitis.
Haploinsufficiency of the canalicular phospholipid floppase Abcb4/Mdr2 sensitizes animals to diet induced injury, generally phenocopying Mdr2 knockout mice as indicated by altered bile composition, elevated peripheral markers of cholestasis, hepatotoxicity and fibrosis, as well as other indicators of hepatic injury.
Abcb4/Mdr2 heterozygous mice subjected to dietary stress present with elevated levels of murine IL-8, increased levels of Cd11b+ cells associated with bile ducts, and elevated markers of fibrosis compared to wild type mice
This newly characterized mouse model represents a more clinically relevant model of bile acid damage in the bile ducts for the evaluation of therapeutic candidates aiming to improve bile composition for the treatment of hepatobiliary diseases like primary sclerosing cholangitis (PSC).
About RTY-694
RTY-694 is an orally acting dual-targeted positive functional modulator (PFM) that addresses the core pathophysiology of primary sclerosing cholangitis (PSC) and multiple hepatobiliary diseases by addressing ABCB4 and BSEP transporter dysfunction to improve bile composition and increase bile flow. In translational mouse models, RTY-694 demonstrated improvements in bile duct health, inflammation and fibrosis. RTY-694 is advancing to first-in-human clinical trials for PSC.
