Ascletis pulls FXR agonist from pipeline over phase 2 primary biliary cholangitis data

China’s Ascletis has been developing the farnesoid X receptor (FXR) agonist ASC42 in a raft of conditions ranging from primary biliary cholangitis (PBC) to metabolic-associated steatohepatitis (MASH).

But the company announced this morning that work is being halted on the drug after getting a glimpse of data from a phase 2 trial of three different doses of ASC42 to treat PBC. The results “indicated that ASC42 did not show competitiveness to new PBC drug candidates currently in development and registrational stages,” the company explained in an April 4 release.

Based on this failure, Ascletis has also decided to drop other programs involving the drug. These include testing the therapy for hepatitis B virus (HBV) as well as part of a combo treatment for MASH.

The biotech, which entered the year with cash and equivalents of 2.4 billion Chinese Yuan ($330 million), attributed today’s decision to “efforts to continue to evaluate and optimize its research and development pipeline to increase efficiency and preserve cash.”

With ASC42 thrown on the discard pile, Ascletis still has more promising options to treat MASH, a fatty liver disease that has previously been known as non-alcoholic steatohepatitis (NASH). At the start of the year, the company’s subsidiary Gannex Pharma linked a THRβ agonist, dubbed ASC41, to significant reductions in liver fat and pointed to findings that it sees providing an edge over Madrigal Pharmaceuticals and Viking Therapeutics.

Viking has previously accused Ascletis of stealing trade secrets to support the development of a drug candidate to rival its MASH prospect VK2809. That dispute rumbled on throughout last year, during which time Gannex continued to work toward midphase data on the molecule at the center of the row. 

Ascletis’ most advanced candidate is ASC22, an injected PD-L1-targeted antibody in phase 2 development as a functional cure for chronic hepatitis B and HIV. The company's clinical-stage pipeline also includes a FASN inhibitor called ASC40 that’s being assessed as a treatment for both MASH and acne, as well as a PD-L1 small molecule inhibitor called ASC61 in early-stage trials for solid tumors.

Part of the savings from discontinuing the various ASC42 programs will be funneled into the continued clinical development of ASC41 and ASC40 for MASH, the biotech explained in today’s release.