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

Author: Benzinga Newsdesk | November 06, 2023 09:52am

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.

 

Integrin αvβ1 is Expressed in Multiple Solid Tumor Types and Drives the Adhesion of Cancer Associated Fibroblast to Latent TGF-β

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.

Selective Targeting of Integrins αVβ8 and αVβ1 within the Dynamic Ecosystem of Pancreatic Cancer to Improve the Overall Anti-tumor Response

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/.

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