Bexotegrast (PLN-74809)


Our lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual-selective inhibitor of αvβ6 and αvβ1 being developed for the treatment of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC).


While expressed at very low levels in normal tissues, αvβ6 and αvβ1 integrins are upregulated in the pulmonary tissues of IPF patients, and in the liver tissues of PSC patients. Both of these integrins serve as activators of TGF-ß, leading to increased collagen production and, ultimately, fibrosis in these tissues. By blocking the activation of TGF-ß by both αvβ6 and αvβ1, we believe bexotegrast (PLN-74809) may slow and potentially halt the progression of fibrosis in these patient populations.

Program Highlights

  • Bexotegrast (PLN-74809) has shown favorable tolerability and pharmacokinetic profile in Phase 1 and Phase 2a trials
  • In a Phase 2a trial, bexotegrast (PLN-74809) demonstrated a dose-dependent treatment effect on FVC and QLF versus placebo over 12 weeks of treatment in patients with IPF
  • In a Phase 2a trial, bexotegrast’s (PLN-74809) treatment effect was observed on top of standard of care therapy and as monotherapy
  • Good oral bioavailability and long half-life are promising for potential once-daily dosing
  • Human biological proof-of-concept shown in a Phase 1b trial in healthy volunteers and a Phase2a trial in patients with IPF
  • Targeting of tissue-specific integrins is designed to maximize antifibrotic effect while avoiding systemic effects of TGF-β inhibition
  • There are currently only two existing FDA-approved therapies for IPF; while both have shown modest slowing of disease progression, medical need remains high
  • There are currently no FDA-approved therapies for PSC

Development Status

  • Topline 12-week data from Phase 2a IPF trial expected early in the first quarter of 2023
  • Topline 24-week data from Phase 2a IPF trial expected early in the first half of 2023
  • Global Phase 2a PSC trial enrolling
  • Topline 12-week data from Phase 2a PSC trial expected in the third quarter of 2023
  • Granted U.S. FDA Fast Track Designation for IPF and PSC
  • Granted U.S. FDA Orphan Drug Designation for IPF and PSC
  • Granted EMA Orphan Drug Designation for PSC

Our Advanced Integrin Library

At Pliant, we have developed an industry-leading library of over 10,000 annotated integrin-binding molecules to probe the molecular drivers of fibrotic disease. With this library, we screen for activity against newly identified targets, to create a deep well of potential drug candidates.

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