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Having explored how the heart is formed in utero, a researcher is reporting how cells and molecules act during that early formation and what might cause the heart disease called left ventricular non-compaction or spongy heart, for which patients often require heart transplants. Having explored how the heart is formed in utero, a University of Houston pharmacology researcher is reporting how cells and molecules act during that early formation and what might cause the heart disease called left ventricular non-compaction. LVNC is a type of heart muscle disease (or cardiomyopathy) also known as a spongy heart, for which patients often require heart transplants. "We found the absence of a certain gene, called Itgb1, may cause inability in the developing heart to maintain its shape and develop normally, causing left ventricular non-compaction," reports Mingfu Wu, associate professor at the UH College of Pharmacy, in Cardiovascular Research. "Itgb1 deletion at an early stage causes distinct defects." Wu's findings involve examination of the trabeculae, which are sheet-like structures in developing hearts that protrude from the heart wall. These structures are crucial in early heart development -- before the coronary system develops -- to supply blood, as they increase the inner surface area of the heart wall and enhance the exchange of oxygen and nutrients between blood and the heart wall. "Without trabeculae, the heart wall would suffer from insufficient oxygen and nutrients, potentially leading to death. Conversely, an excess of trabeculae can result in an overly porous heart wall, leading to left ventricular non-compaction cardiomyopathy, commonly known as spongy heart," said Wu. While certain signals controlling trabeculae formation are known, the precise mechanisms by which individual cells that make up the cardiac muscle (cardiomyocytes) are organized to form these structures remain unclear. "This study reveals that deleting a gene called Itgb1 in heart wall cardiomyocytes prevents trabeculae formation. We found that the protein β1 integrin encoded by Itgb1 and its ligands, the extracellular matrix, create a molecular network that acts as a scaffold for cardiomyocytes in the heart wall. When Itgb1 is deleted, cardiomyocytes disengage from this scaffold, losing their ability to maintain shape, divide properly, migrate, and form trabeculae," said Wu. The study suggests that the molecular network may be a common organizational mechanism in organ formation. "We believe these insights will greatly interest researchers in organ development and regeneration, potentially reshaping our understanding of tissue organization and development," said Wu. Wu's collaborators from the University of Houston include Lianjie Miao, Yangyang Lu, Anika Nusrat, Luqi Zhao Micah Castillo, Yongqi Xiao, Hongyang Guo, Yu Liu, Preethi Gunaratne, Robert, J Schwartz, Alan R Burns, Ashok Kumar and C. Michael DiPersio, Albany Medical College.

Presentations highlight preclinical and clinical advancements of bexotegrast program in primary sclerosing cholangitis SOUTH SAN FRANCISCO, Calif., June 23, 2023 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX), a clinical stage biotechnology company focused on discovering and developing novel therapeutics for the treatment of fibrosis, today announced that it presented Phase 2a clinical data and preclinical data of bexotegrast (PLN-74809) program this week as part of the European Association for the Study of the Liver (EASL) International Liver Congress™ 2023, held June 21- 24, 2023. Bexotegrast, is an oral, small molecule, dual-selective inhibitor of αvβ6 and αvβ1 integrins being developed for the treatment of idiopathic pulmonary fibrosis and primary sclerosing cholangitis (PSC). “PSC is a rare chronic autoimmune disease with no effective therapy, representing a large unmet need for new treatments. Our presentations this week discuss the early non-clinical work that support our ongoing Phase 2a clinical program. We look forward to sharing interim data from this trial in the third quarter,” said Éric Lefebvre, M.D., Chief Medical Officer at Pliant Therapeutics. INTEGRIS-PSC Phase 2a Study: Evaluating the Safety, Tolerability, and Pharmacokinetics of Bexotegrast (PLN-74809) in Participants with Primary Sclerosing Cholangitis The study design, baseline demographics and blinded safety data from the 85 participants randomized into the 40, 80 and 160 mg dose cohorts or placebo was presented from the ongoing INTEGRIS-PSC Phase 2a study. This study is evaluating the safety, tolerability, and pharmacokinetics of bexotegrast in PSC. Twelve-week data from this study is expected in the third quarter of 2023. Following a positive independent Data Safety Monitoring Board (DSMB) safety review in the first quarter, enrollment commenced in a Phase 2a trial of bexotegrast at 320 mg dosed once daily for at least 24 weeks, and up to 48 weeks, in patients with PSC. The following posters were selected for inclusion in EASL’s Session Poster Tours. Dual alpha-v/beta-6 and alpha-v/beta-1 Integrin Inhibitor Bexotegrast Attenuates Profibrogenic Gene Expression of Myofibroblasts in Human Liver Explant Tissue with Biliary Fibrosis The effects of bexotegrast on individual cell populations were evaluated in fibrotic PSC and primary biliary cholangitis (PBC) precision-cut liver slices. Treatment with bexotegrast resulted in clear reductions in profibrogenic gene expression across multiple pathologic cell populations with a similar degree of reduction in profibrogenic gene expression seen compared to a TGF-β receptor I kinase inhibitor. These results suggest an important role for the integrin-TGF-β activation pathway in fibrotic biliary diseases and are consistent with the anti-fibrotic mechanism of action of bexotegrast. Non-invasive Imaging Method Demonstrates Anti-fibrotic Efficacy of a Dual Integrin alpha-v/beta-6 and alpha-v/beta-1 Inhibitor in a Rat Model of Biliary Fibrosis PET and molecular MRI were used to non-invasively monitor the effects of αvβ6 and αvβ1 antagonism in a rat model of biliary fibrosis. Results showed changes in target expression and fibrosis in response to bile duct injury and treatment with a dual integrin αvβ6/αvβ1 antagonist that were confirmed by classic histological analysis. These data support the antifibrotic effect of dual αvβ6/αvβ1 integrin inhibition in biliary fibrosis. Posters presented at the 2023 EASL Conference are available under the Publications section on Pliant’s website at https://pliantrx.com/publications. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those regarding future development of bexotegrast and timing of future data from our clinical programs. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant Therapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the development and commercialization of our product candidates, including any delays in our ongoing or planned preclinical or clinical trials, the impact of the COVID-19 pandemic on our business, operations, clinical supply and plans, our reliance on third parties for critical aspects of our development operations, the risks inherent in the drug development process, the risks regarding the accuracy of our estimates of expenses and timing of development, our capital requirements and the need for additional financing, and our ability to obtain and maintain intellectual property protection for our product candidates. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Annual Report on Form 10-K for the year ended December 31, 2022, as updated by our Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, which are available on the SEC's website at www.sec.gov. Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. About Pliant Therapeutics, Inc. Pliant Therapeutics is a clinical stage biopharmaceutical company focused on discovering and developing novel therapies for the treatment of fibrosis. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral small molecule dual selective inhibitor of αvß6 and αvß1 integrins that is in development in the lead indications for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in IPF and PSC and Orphan Drug Designation from the European Medicines Agency in IPF and PSC. Pliant is currently conducting a Phase 2a trial of bexotegrast in the PSC and is planning a Phase 2b trial in IPF. Pliant has also developed PLN-1474, a small molecule, selective inhibitor of αvß1 for the treatment of nonalcoholic steatohepatitis, or NASH with liver fibrosis. Pliant is initiating a Phase 1 study for its third clinical program, PLN-101095, a small molecule, dual-selective inhibitor of αvß8 and αvß1 integrins, that is being developed for the treatment of solid tumors. In addition to clinical stage programs, Pliant currently has a preclinical program targeting muscular dystrophies. For additional information, please visit: www.PliantRx.com. Follow us on social media: Twitter, LinkedIn, Facebook and YouTube. Investor and Media Contact: Christopher KeenanVice President, Investor Relations and Corporate CommunicationsPliant Therapeutics, Inc.ir@pliantrx.com