Novartis takes $80M punt on early-stage NASH drug from Pliant

Novartis has added another non-alcoholic steatohepatitis (NASH) drug candidate to its pipeline via an $80 million licensing deal with US biotech Pliant Therapeutics.

The agreement focuses on PLN-1474, a preclinical-stage drug that works as a small-molecule inhibitor of integrin αVβ1, a target that is thought to be involved in the development of fibrotic (scar) tissue in the livers of people who develop NASH.

Novartis is making the cash payment upfront in return for rights to PLN-1474 and options on up to three more integrin-targeting compounds in Pliant’s pipeline, and will also take an undisclosed equity stake in the South San Francisco-based biotech.

NASH is a severe form of non-alcoholic fatty liver disease (NAFLD), in which a build-up of fat in the liver – typically associated with obesity, diabetes and high cholesterol – triggers a vicious cycle of chronic inflammation and fibrosis.

If left unchecked, that cycle can progress to cirrhosis, which raises the risk of liver cancer, liver failure and death.

The promise of big rewards for a successful drug treatment of NASH has spurred dozens of drug developers to try to develop the first therapy for the disease, which affects millions of people worldwide and has been tipped to become a $20-$35 billion market.

Novartis has made NASH a key pipeline priority, but it has proved a challenging target and already resulted in a number of failed clinical trials. That includes emricasan, a drug Novartis licensed form Conatus that failed mid-stage testing, as well as other candidates including Gilead’s selonsertib and Takeda/Shire’s SHP626 (volixibat).

At the moment Intercept is in pole position to get a NASH therapy to market, having filed for approval of its obeticholic acid drug for NASH with fibrosis on the strength of a positive phase 3 trial. That looks set to get a verdict from the FDA in around March of next year.

Novartis already has NASH partnerships in place with Pfizer and Allergan, agreed last year and in 2017, respectively, and added to its pipeline in April by purchasing NASH specialist IFM Tre in a deal valued at up to $1.75 billion.

The Swiss group already has two candidates for the disease in clinical trials – FXR agonist tropifexor and a fixed-dose combination of tropifexor with CCR2/5 inhibitor cenicriviroc.

Under the terms of the latest deal, Pliant will be responsible for development of PLN-1474 through phase 1, after which Novartis will assume responsibility for all future work on the project. Novartis will also fund the research on the drug.

Pliant says it expects to file for approval to start clinical trials of the drug before the end of the year.

RAS inhibitor collaboration

Meanwhile, Novartis has just penned another pipeline-boosting deal, this time in the cancer area. It has joined forces with Cancer Research UK's Beatson Institute to work on inhibitors of RAS, a gene which is often mutated in malignant cells.

More than 30% of all human cancers, including 95% of pancreatic and 45% of colorectal tumours, are linked to RAS mutations, but so far no drugs have been developed that have been able to target them effectively.

Novartis will collaborate with the Beatson team to develop RAS inhibitors discovered at the institute, and has the option to exclusively license the compounds. It's making an undisclosed upfront payment and will also fund the research.