Selonsertib

"*" indicates required fields Viscient Bio, Inc. has announced it has identified the world’s first drug candidate discovered primarily using 3D bioprinted tissue models of disease formed from human cells. The company said it expects to develop the drug to treat non-alcoholic steatohepatitis (NASH), a growing epidemic disease that is believed to affect more than 10% of the U.S. population. NASH can often lead to hepatocellular carcinoma or liver failure. Due to the devastating effects of NASH on patients and its wide prevalence, analysis has projected future pharma industry revenues for the drug in the tens of billions of dollars per year. Viscient Bio’s lead compound is an orally-delivered small molecule designed to hit a novel target identified in 3D bioprinted and other 3D tissue models of disease. In preclinical studies, the drug has proven to be well tolerated. In Viscient Bio’s models of disease, the compound shows reduction of fibrosis as measured by histological evidence similar to that used for human liver biopsy. Using the same model, fibrosis reduction is also seen for obeticholic acid and resmetirom, while no fibrosis reduction is seen for drugs such as cenicriviroc, selonsertib, and elafibranor. The newly discovered target is predominantly expressed in liver tissue. “It is long past time to displace the model of drug development reliant on proof of activity in animals,” said Viscient Bio chief executive officer Keith Murphy. “Viscient’s trailblazing work has resulted in 3D cellular human models of disease in which the performance of previously tested compounds has matched clinical results. Failed NASH drugs never would have been put in humans based on what can be clearly seen in these models. Our novel compound shows fibrosis reduction in these models, as do NASH drugs known to work in phase 3, and we are excited to move this lead program forward.” The lead compound’s clear reduction of fibrosis in Viscient Bio’s NASH models is promising because Viscient Bio’s 3D models of NASH have shown extremely high correlation with clinical results in patients. The model demonstrates fibrosis reduction for known clinical compounds tested by pharma companies that have that effect in humans, while revealing lack of fibrosis reduction for compounds that failed in phase 2 or phase 3 for NASH. The model is accurate in predicting both successes and failures among clinical compounds tested to date. The gene expression of Viscient Bio’s models is also well correlated with that seen in disease samples from patients. Though tested post-hoc, the results are not backfit, as the model was finalized before testing of any clinical compounds was conducted. According to the Biotechnology Innovation Organization’s 2021 report, only 7.9% of drugs that enter clinical trials are approved for human use. Viscient Biosciences said it believes it can achieve a significantly better clinical translation rate using more relevant 3D human tissue models of disease, leading to more successes and lower drug development costs per approved drug. Viscient Biosciences’ lead compound is expected to enter the clinic in 2024.

Genfit now has three candidates aimed at acute-on-chronic liver failure. 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.