RTY-694 increased protein levels and function of ABCB4 and BSEP in primary hepatocytes,
two transporters that play a key role in bile composition and bile flow
Data demonstrate the potential of PFMs to restore and enhance membrane protein function in addition to characterizing a novel preclinical translational model of cholangitis and cholestasis
CAMBRIDGE, Mass. – November 18, 2024 [Globe Newswire] – Rectify Pharmaceuticals, Inc., (“Rectify”) 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, taking place in San Diego, CA, November 15 – 19, 2024.
“Building on the momentum of our recent nomination of RTY-694 as our lead candidate for the treatment of primary sclerosing cholangitis and other hepatobiliary diseases, we are proud to present compelling translational data,” said Rajesh Devraj, Ph.D., President and Chief Executive Officer of Rectify. “These data continue to substantiate the potential of a dual-targeted ABCB4/BSEP PFM to address the dysfunction of these two membrane protein transporters and offer a differentiated approach to address cholangitis and cholestasis by improving bile composition and enhancing bile flow.”
Title: Identification and in vitro characterization of a novel BSEP and ABCB4 dual-acting positive functional modulator targeting the treatment of a broad range of hepatobiliary diseases.
Abstract Number: 4367
Presenter: Jennifer Truong, Ph.D., Rectify Pharmaceuticals
Session Title: Human Cholestatic and Autoimmune Liver Diseases
Session Date and Time: Monday, November 18, 2024, from 1:00 p.m. to 2:00 p.m. PST
Key findings
- 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.
Title: Abcb4/Mdr2 haploinsufficiency predisposes mice to biliary injury and secondary cholestasis and defines a translational model of toxic bile induced hepatobiliary injury in human cholangiopathy
Abstract Number: 4018
Presenter: Eric Bell, Ph.D., Rectify Pharmaceuticals
Session Title: Biliary Physiology, Transport, Cholangiocyte Biology, and Experimental Cholestasis
Session Date and Time: Monday, November 18, 2024, from 1:00 p.m. to 2:00 p.m. PST
Key findings
- 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).
Both posters will be available on the Rectify website at https://rectifypharma.com/publications/.
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.
About Rectify Pharmaceuticals, Inc. (“Rectify”)
Rectify is advancing Positive Functional Modulators (PFMs), a novel class of oral, small molecules that restore and enhance membrane protein function to address the underlying cause of serious diseases. Rectify’s PFMs have potential to modulate the activity of wild-type and mutated membrane bound proteins, a historically difficult challenge with a small molecule approach. The Company’s breakthrough product platform enables efficient and rapid discovery of first- and best-in-class small molecule therapies with the potential to address membrane protein dysfunction for treatment of rare and common diseases, including liver, cardio-renal-metabolic, and neurodegenerative diseases. Rectify was founded and seeded by Atlas Venture who co-led the $100M Series A round with Omega Funds and were joined by Forbion and Longwood Fund.
For more information, please visit www.rectifypharma.com or follow us on X and LinkedIn.
Contact
Media
Michael Rubenstein
LifeSci Communications
+1 646-386-1613
mrubenstein@lifescicomms.com