Genfit Advances Nangibotide Toward Phase 2 for Acute-on-Chronic Liver Failure
Key Facts
On November 9, 2026, Genfit announced a package of prior clinical data supporting the development of nangibotide as it advances to Phase 2 for acute-on-chronic liver failure, known as ACLF. The company said its clinical experience included 416 people exposed to the drug, including participants in three Phase 2 studies in septic shock and COVID-19. It added that the safety profile was similar to placebo, with no safety signal observed. The announcement puts the drug on track for a trial dedicated to patients with ACLF, but does not represent results from a new trial conducted in this disease. It was also not possible to verify the company's share-price movement or percentage change in the November 9 session.
In earlier septic-shock data, Genfit presented results from a subgroup of 118 patients with elevated sTREM-1 levels. The company said the decline in SOFA score among those who received nangibotide exceeded the decline in the placebo group by 2.5 points on day 5. The score measures the severity of organ dysfunction, and the company said the respiratory, cardiovascular and kidney components showed statistically significant improvement. The company described these data as part of the drug's prior clinical record, not evidence from patients with ACLF. Their use to support moving to a new study comes as the drug is being tested in a different patient population.
The company also cited data involving 219 patients with COVID-19, in which nangibotide use was associated with improved clinical status and lower mortality by day 28. These findings, like the septic-shock data, are part of the prior experience on which Genfit is basing the drug's development. This context differs from ACLF, the disease targeted by the next program, so the data do not constitute proven evidence of treatment efficacy in patients with acute-on-chronic liver failure. The company presents these signals as clinical support for moving to a trial in the new disease. The announced evidence package is intended to prepare for that transition, not to announce the success of a Phase 2 trial in ACLF.
Genfit plans to conduct the UPWARD study as a randomized, placebo-controlled proof-of-concept trial targeting patients with grade 2 ACLF and bacterial infections. Under the company's design, participants will be allocated at a 2:1 ratio between nangibotide and placebo, with a continuous intravenous infusion lasting 3 to 7 days alongside standard care. The company has set safety as the primary objective and pharmacokinetics as secondary objectives, while exploratory endpoints will look for signals of efficacy. This design means the planned trial will primarily assess safety, while efficacy measures remain exploratory. Jennifer Lai, a liver transplant specialist at the University of California, San Francisco, said the unmet medical need is substantial, particularly for intensive-care patients whose disease may progress rapidly to multiple organ failure, noting that the drug's entry into this field draws on its prior clinical experience.
According to Genfit, nangibotide modulates the TREM-1 pathway, which the company considers an amplifier of inflammation, with the aim of limiting amplification of an excessive inflammatory response without directly targeting immune recognition. Before the event, the company had announced that the data presentation would take place on November 8, 2026, and that the clinical package would support advancing the drug to Phase 2 in ACLF. Genfit expects the UPWARD trial to begin by the end of 2026, subject to regulatory approval. It also expects initial data in the second half of 2027. Both dates remain company forecasts, while the planned study represents the next step in testing nangibotide in patients with ACLF.