Pliant Therapeutics Presentations at the Annual Meeting of the Society for Immunotherapy of Cancer Highlight PLN-101095, A Novel Inhibitor of Integrins αvβ8 and αvβ1
SOUTH SAN FRANCISCO, Calif., Nov. 06, 2023 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX), a clinical-stage biotechnology company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases, presented three posters highlighting PLN-101095, a novel inhibitor of integrins αvβ8 and αvβ1. These posters were presented as part of the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) held November 1 - 5, 2023.
Trial in Progress: Phase 1a Trial of PLN-101095, an Integrin αvβ8 and αvβ1 Inhibitor, as Monotherapy and in Combination with Pembrolizumab, in Treatment-resistant Patients with Advanced or Metastatic Solid Tumors
Pliant is conducting a first-in-human, open-label, dose-escalation study designed to evaluate the safety, tolerability, and pharmacokinetics of PLN-101095 as monotherapy and in combination with pembrolizumab in adult patients with advanced or metastatic solid tumors and documented disease progression after at least 3 months from the start of treatment with pembrolizumab, and with no other available effective treatment options.
Expression of αvβ1 protein was evaluated across a diverse set of human tumor tissues and cancer-associated fibroblasts (CAF) to investigate its functional role in cancer biology. PLN-101095, a selective small molecule inhibitor of αvβ8 and αvβ1 integrins, was evaluated in combination with anti-mPD-1 on fibrotic markers in the EMT6 tumor model. PLN-101095 was shown to block the binding of cancer-associated fibroblasts (CAF) to the TGF-β latency-associated peptide (LAP) in a dose-dependent manner. EMT6 tumor tissues treated with PLN-101095 and anti-mPD-1 showed a significant reduction in fibrotic markers compared to anti-αvβ8 and anti-mPD-1. PLN-101095 was also shown to effectively reduce the expression of the fibroblast activation marker αSMA in ex vivo-treated human breast tumor tissues.
PLN-101095, a selective small molecule inhibitor of αvβ8 and αvβ1 integrins, was assessed in preclinical models of pancreatic ductal adenocarcinoma (PDA). PLN-101095 was shown to decrease primary tumor growth, improve chemosensitivity in metastatic PDA with gene expression changes associated with favorable immune response and improved prognosis. Results showed that selective targeting of αvβ8 and αvβ1 with PLN-101095 or αvβ1 signaling with PLN-76104 potently inhibited primary tumor growth, spread and improve chemotherapy response in models of PDA.
These posters are available on the Publications page of the Pliant’s website at https://pliantrx.com/publications/.
About Pliant Therapeutics, Inc.
Pliant Therapeutics is a clinical-stage biopharmaceutical company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases. 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 has initiated BEACON-IPF, a Phase 2b trial of bexotegrast in IPF. Pliant has also developed PLN-1474, a small molecule, selective inhibitor of αvß1 integrin for the treatment of nonalcoholic steatohepatitis, or NASH with liver fibrosis. Pliant has initiated 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 X, LinkedIn, Facebook and YouTube.
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