MDR3

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., Nov. 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: 4367Presenter: Jennifer Truong, Ph.D., Rectify PharmaceuticalsSession Title: Human Cholestatic and Autoimmune Liver DiseasesSession 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: 4018Presenter: Eric Bell, Ph.D., Rectify PharmaceuticalsSession Title: Biliary Physiology, Transport, Cholangiocyte Biology, and Experimental CholestasisSession 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 miceThis 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-694RTY-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 MediaMichael RubensteinLifeSci Communications+1 646-386-1613mrubenstein@lifescicomms.com

CAMBRIDGE, Mass., Nov. 12, 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 that it will host a virtual R&D event on Thursday, November 21, 2024, from 11:00 AM to 1:00 PM EST. To register, click here. The R&D event, titled “Rectifying Protein Dysfunction: RTY-694 for the Treatment of Primary Sclerosing Cholangitis (PSC)”, will discuss PFMs as a novel small molecule modality to restore and enhance protein function, the role of ABCB4 and BSEP transporter proteins in driving the core pathophysiology of PSC, clinical presentation and unmet need in PSC, and advancement of RTY-694, an orally available ABCB4/BSEP dual targeted PFM for the treatment of PSC, toward the clinic. The event will feature presentations from the following key opinion leaders (KOLs): Robert A. Copeland, PhD – Rectify Scientific Advisory Board member and President and CSO of Accent TherapeuticsKris Kowdley, MD, FACP, FACG, AGAF, FAASLD – Professor at Elson S. Floyd College of Medicine at Washington State UniversityRichard J. Thompson, BM BCh, DM – Rectify Scientific Advisory Board member and Professor at Institute of Liver Studies at King’s College London Company management will also provide an overview of Rectify's breakthrough PFM product platform, additional programs and future directions. A live question and answer session will follow the formal presentations. About Robert A. Copeland, PhD Robert A. Copeland, PhD, is a Rectify Scientific Advisory Board member and the co-founder of Accent Therapeutics and serves as its President and Chief Scientific Officer. He is also President of the independent consulting firm, Ki Consultant, LLC. He was formerly President of Research and Chief Scientific Officer of Epizyme, Inc. and before that, Vice President of Cancer Biology in the Oncology Center of Excellence in Drug Discovery at GlaxoSmithKline. Dr. Copeland serves on a number of advisory boards within industry, academia, professional societies and professional journals. His research interest is in elucidating the determinants of drug recognition by their biological targets and the use of this information in the discovery and design of new medicines. He has contributed to drug discovery and development efforts leading to 20 investigational new drugs entering human clinical trials. Dr. Copeland has contributed to more than 200 scientific publications, holds 14 issued US patents and has authored six books in the areas of protein science and enzymology. He is a member of the editorial boards of Molecular Cancer Therapeutics (AACR) and ACS Medicinal Chemistry Letters. Dr. Copeland received his Doctorate in chemistry from Princeton University and completed postdoctoral studies as the Chaim Weizmann Research Fellow at the California Institute of Technology. He was elected a Fellow of the American Association for the Advancement of Science (AAAS) and of the Royal Society of Chemistry. About Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD, is Director of Liver Institute Northwest and Professor, Elson S. Floyd College of Medicine at Washington State University. He received his B.S. in Biology and Anthropology from Columbia University, and his medical degree from Mount Sinai School of Medicine. He completed his internship and residency at Oregon Health Science University and a Fellowship in Gastroenterology and Hepatology at Tufts University School of Medicine. Dr. Kowdley is internationally recognized as a clinician, educator, and researcher in liver disease. He has led several major international clinical trials of new treatments for hepatitis C, primary biliary cholangitis, primary sclerosing cholangitis and nonalcoholic steatohepatitis. Dr. Kowdley is the author of more than 1,000 articles, book chapters, reviews, abstracts and commentaries, and his scholarly work has been cited more than 70,000 times (h-index 123), according to Google Scholar. He is on the Web of Science list of “Highly Cited Researchers” (top 1% by citations for field) for 2019-2023. About Richard J. Thompson, BM BCh, DM Richard J. Thompson, BM BCh, DM, is a Rectify Scientific Advisory Board member and the Professor of Molecular Hepatology at King’s College London and honorary Consultant Pediatric Hepatologist at King’s College Hospital, London. He specializes in pediatric liver disease and is particularly interested in genetic liver diseases in both children and adults. Through worldwide collaborations, his lab continues to identify new causes of genetic liver disease. Additionally, Dr. Thompson served as the clinical lead for genomics and the 100,000-genome project at King’s College Hospital and is the clinical lead for the diagnostic laboratory specializing in liver and gastrointestinal disease. He has been the principal investigator on several clinical trials. Dr. Thompson has published over 70 peer reviewed articles, as well as book chapters and editorials. He has been an invited speaker at numerous conferences worldwide. Dr. Thompson received his undergraduate medical and research degrees from the University of Oxford. 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 MediaMichael RubensteinLifeSci Communications+1 646-386-1613 mrubenstein@lifescicomms.com

RTY-694 is a potent, orally active ABCB4/BSEP positive functional modulator (PFM) that improves bile composition and enhances bile flow The differentiated mechanism of a dual-targeted ABCB4/BSEP PFM addresses the underlying pathophysiology of cholestasis and cholangitis associated with multiple hepatobiliary diseases, including primary sclerosing cholangitis RTY-694 improved bile composition and demonstrated reductions in bile duct injury, cholestasis, inflammation and fibrosis Oct. 22, 2024 -- Rectify Pharmaceuticals, Inc., (“Rectify”) a biotechnology company developing positive functional modulators (PFMs), small molecule therapeutics that restore and enhance membrane protein function, today announced that RTY-694 was selected as the lead PFM for its hepatobiliary program and is advancing to first-in-human clinical trials for primary sclerosing cholangitis (PSC). “Rectify was founded to harness the untapped therapeutic potential of restoring or enhancing membrane protein function to address the underlying drivers of disease. The selection of RTY-694 as our lead candidate for the treatment of PSC marks an important milestone for our company and validates our breakthrough proprietary PFM platform for developing therapies that restore and enhance membrane protein function,” said Rajesh Devraj, Ph.D., President and Chief Executive Officer of Rectify. “With this lead candidate nomination and a strong pipeline of earlier stage programs for cardio-renal-metabolic and neurodegenerative diseases, we are poised to establish PFMs as a novel small molecule modality and Rectify as the industry-leading PFM company.” Pol Boudes, M.D., Chief Medical Officer of Rectify, added “We believe our differentiated dual-targeted approach of addressing ABCB4 and BSEP transporter dysfunction to improve bile composition and enhance bile flow has the potential to rectify the core pathophysiology of PSC and multiple hepatobiliary diseases. We look forward to advancing RTY-694 to first-in-human clinical trials as we pursue our mission of helping patients with serious diseases.” PSC is a debilitating orphan bile duct disease characterized by inflammation, fibrosis, and narrowing of the medium and large intra- and extra-hepatic bile ducts that leads to cholangitis, cholestasis and ultimately liver failure. Patients living with PSC experience a high symptom burden that reduces their quality of life and often requires hospitalization. They also face a 400-fold higher rate of developing cholangiocarcinoma, a bile duct cancer, compared to the general population. Many patients will eventually require liver transplant due to disease progression and complications. There are currently no approved medications for the treatment of PSC. RTY-694 is an orally acting dual-targeted PFM that addresses the core pathophysiology of PSC disease progression by increasing the function of the ABCB4 and BSEP transporters, two membrane proteins that play a critical role in maintaining bile composition and bile flow. In translational mouse models, RTY-694 demonstrated improvements in bile duct health, inflammation and fibrosis including: Increases in biliary phospholipids, a key bile component that buffers inflammatory free cholesterol and detergent bile acids Reductions in serum bile acids, ALT and ALP levels Improvements in ductular reaction characterized by a reduction in cholangiocyte proliferation and inflammation Reductions in TGF-β activation and periportal fibrosis 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. The content above comes from the network. if any infringement, please contact us to modify.