Novartis bets $80M on Pliant's preclinical NASH prospect

Novartis has put up an initial $80 million to land the global license to Pliant Therapeutics’ preclinical nonalcoholic steatohepatitis (NASH) asset and three additional candidates. The NASH drug, PLN-1474, is a small molecule inhibitor of integrin αVβ1 Pliant thinks can reduce the growth of fibrotic tissue in the liver. 

South San Francisco-based Pliant is best known for its work to treat idiopathic pulmonary fibrosis by inhibiting the integrins αVβ6 and αVβ1. That program yielded phase 1b data over the summer, setting Pliant up to move into phase 2a later in the year, and underpinned an earlier $62 million series B round. In parallel, Pliant has worked to apply its knowledge of integrin inhibitors to late-stage liver fibrosis.

“NASH is a difficult disease to tackle, and most compounds currently in development are targeting metabolic targets that address earlier stages of disease. PLN-1474 utilizes a fundamentally different mechanism from liver metabolism targeting drugs,” Pliant CEO Bernard Coulie said. 

The liver program has caught the attention of Novartis. Under the terms of the deal unveiled today, Novartis will pay an initial $80 million in the form of an upfront fee and commitments to invest in its new partner. In return, Novartis will get the global rights to PLN-1474 and drugs against up to three additional integrin targets that Pliant will work on as part of the collaboration.

Pliant plans to file an IND for PLN-1474 by the end of the year and will be responsible for taking the drug through phase 1. Beyond that, Novartis will step in and take responsibility for development, manufacturing and commercialization, making milestone payments to Pliant as the drug advances. 

The potential of PLN-1474 to stand out in a crowded field littered with more advanced rivals rests on its novel mechanism of action. Unlike many NASH candidates, PLN-1474 is designed to directly target fibrosis. Pliant aims to reduce liver fibrosis by acting on αVβ1, an integrin implicated in the activation of TGF-β and the scarring of the liver that leads some NASH patients to require transplants. 

“It is a selective inhibitor of the integrin αVβ1 which results in a profound, direct antifibrotic affect. This approach addresses the later stages of NASH which are currently not being treated with the compounds in clinical development. Moreover, Pliant’s approach of selective integrin inhibition results in a liver tissue-specific antifibrotic effect which mitigates potential tolerability risks,” Coulie said. 

Over the past year, Pliant has presented preclinical data to support its hypothesis, starting with tests in mice that linked αVβ1 inhibition to a significant reduction in liver fibrosis. A subsequent study found inhibition of αVβ1 reduced expression of genes related to fibrosis in human NASH liver slices. 

The data provided early validation of Pliant’s belief that inhibiting αVβ1 can stop NASH patients from progressing to cirrhosis and the liver-related complications it entails. Novartis will be the beneficiary if Pliant is right.