PLN-1474

Pipeline

PLN-1474 is an oral, small-molecule selective inhibitor of αvβ1; in development for treatment of stage F3/F4 liver fibrosis associated with nonalcoholic steatohepatitis, or NASH.

About PLN-1474

NASH is a more severe form of non-alcoholic fatty liver disease, or NAFLD. NASH is highly prevalent, affecting approximately 16.5 million adults in the United States, including approximately 3.3 million with stage F3/F4 fibrosis. The stage of fibrosis is the strongest predictor of liver-related morbidity and all-cause mortality in NASH. Patients with F3 and F4 fibrosis carry liver-related mortality risk that is 17 times and 42 times greater, respectively, than NASH patients without fibrosis. Therefore, we believe that treating F3/F4 liver fibrosis will have an impact on liver-related morbidity and all-cause mortality in NASH.

Integrin αvβ1 serves as an activator of TGF-ß and its expression has been shown to be upregulated in activated hepatic stellate cells and correlated with severity of liver fibrosis. By inhibiting αvβ1, we believe PLN-1474 could have a potent direct antifibrotic effect in advanced liver fibrosis.

Program Highlights

  • Proven mechanism in NASH/liver fibrosis
    • Preclinical activity in animal models of NASH-fibrosis (CCl4 – CDA-HFD)
    • Potent antifibrotic effect observed in live human NASH liver tissue
  • Favorable drug properties & pharmacokinetics
    • Orally bioavailable with preclinical PK suggesting BID or better oral dosing
    • Highly potent and highly selective: >100-fold αvβ1 selectivity vs. other integrins
  • Partnered with Novartis in October 2019

Development Status

  • First-in-human Phase 1 healthy volunteer trial currently underway
  • Preliminary data expected in early 2021
  • PLN-1474 transferred to Novartis for future development

Our Advanced Integrin Library

At Pliant, we have developed an industry-leading library of over 7,000 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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