DENVER, November 9, 2026 — Genfit has advanced its TREM-1 modulator, nangibotide, into acute-on-chronic liver failure (ACLF) with Phase 2 data expected in 2027. This development comes after prior Phase 2 trials showed safety signals in septic shock and severe COVID-19.
Understanding Acute-On-Chronic Liver Failure
Acute-on-chronic liver failure is a syndrome in patients with chronic liver disease characterized by acute hepatic decompensation, organ failures, and high short-term mortality. It is driven by excessive systemic inflammation that leads to multi-organ failure, particularly in ICU patients. For families and patients affected by this condition, the lack of effective treatments means a poor prognosis and limited options.
Nangibotide And Its Mechanism
Nangibotide is designed to dampen excessive inflammatory amplification without directly targeting immune recognition. It works by modulating the TREM-1 pathway, which has been associated with disease severity and adverse outcomes in ACLF. The TREM-1 pathway activation has been reported as patients progress from acute decompensation to acute-on-chronic liver failure.
Prior Phase 2 Data And Upcoming Trials
Prior Phase 2 data showed an overall safety profile similar to placebo with no safety signal identified. Efficacy signals included improved clinical status and lower mortality in a subgroup of septic shock patients and in patients with severe COVID-19. The UPWARD Phase 2a proof-of-concept trial in ACLF is expected to initiate by the end of 2026, with topline data expected in the second half of 2027. According to Professor Jennifer Lai of UCSF, the program benefits from substantial Phase 2 experience in acute inflammatory conditions with organ dysfunction.
What This Means For Patients
For patients with ACLF, the advancement of nangibotide into Phase 2 trials offers hope for a potential new treatment. The human side of this development is significant, as it may lead to improved outcomes and reduced mortality for those affected by this condition. As Professor Lai noted, the unmet need in ACLF remains tremendous, particularly for patients in the ICU who can rapidly progress to multi-organ failure. The development of nangibotide is a step towards addressing this need, and its potential impact on patients’ lives is substantial.
On November 8, 2026, Genfit presented the nangibotide clinical package at a scientific event during AASLD The Liver Meeting in Denver. Talk to your doctor or hepatologist about the latest developments in ACLF treatment and the potential of nangibotide.
Sources
- GENFIT Highlights Data from Clinical Studies of Nangibotide, Supporting Its Advancement into ACLF with Phase 2 Data Expected in 2027
- Genfit details its ACLF strategy and MASH diagnostics at the AASLD congress
- GENFIT Highlights Data from Clinical Studies of Nangibotide, Supporting Its Advancement into ACLF with Phase 2 Data Expected in 2027
- GENFIT Highlights Data from Clinical Studies of Nangibotide, Supporting Its Advancement into ACLF with Phase 2 Data Expected in 2027
Photo: Jair Lázaro / Unsplash (Unsplash License)
