Genfit has added a third liver failure candidate to its portfolio courtesy of a licensing deal with Seal Rock Therapeutics potentially worth up to 100 million euros ($107 million) in biobucks.
The asset in question is an injectable form of Seal Rock’s ASK1 inhibitor SRT-015, for which Genfit has secured the rights in liver disease. France-based Genfit has its sights set on entering the clinic with the candidate in the second half of next year, with a proof-of-concept study in acute-on-chronic liver failure (ACLF) penciled in for 2025.
Apoptosis signal-regulating kinase 1 (ASK1) is a member of the MAP kinase family. Inhibiting ASK1 has been shown to block lipopolysaccharide-associated hyperinflammatory response as well as reduce the release of proinflammatory cytokines, reduce fibrosis and protect macrophage mitochondrial function, Genfit explained in the postmarket release yesterday.
Animal models and clinical trials have already shown benefits of this mechanism across a wide range of organ diseases, including of the kidney, liver, brain and cardiopulmonary system, the biotech added.
These drugs haven’t always lived up to the hype, however. Gilead’s ASK1 inhibitor selonsertib flunked a couple of phase 3 trials in nonalcoholic steatohepatitis, the same condition for which Seal Rock had been developing SRT-015.
Eyeing an ACLF market estimated to total $4 billion in the U.S. and five major European countries alone, the Seal Rock deal means Genfit now has three candidates targeting this space. Those include VS-01, which is in a phase 2 trial for adults with ACLF grades 1 and 2 and ascites, as well as NTZ, which has completed a pair of phase 1 studies in renal and hepatic impairment. Genfit is now readying NTZ for a phase 2 in ACLF.
Genfit CEO Pascal Prigent said today’s licensing agreement “marks an additional milestone in the execution of our development strategy in liver diseases with high unmet medical needs.”
“ACLF is a complex disorder that will likely require the combination of different approaches and with this acquisition, we continue to strengthen our leadership in this indication,” Prigent added. “Considering its liver-centric activity, the potential for multi-organ benefits and the breadth of evidence supporting further development in ACLF, we strongly believe in the potential of SRT-015.”
While no upfront payment was mentioned in the release, Seattle-based Seal Rock is in line for up for 100 million euros in regulatory, clinical and commercial milestone payments alongside tiered royalties.
Genfit’s remaining therapeutic pipeline includes the dual PPAR agonist elafibranor, which is undergoing late-stage studies for primary biliary cholangitis and has been licensed by Ipsen. There’s also GNS561, a PPT1 inhibitor that has previously completed a phase 1 trial and is now being developed for bile duct cancer, and VS-02, a preclinical urease inhibitor the biotech hopes to progress for hepatic encephalopathy.