Genfit details Nangibotide in ACLF, first Phase 2a data expected in 2027
On November 8, 2026, in Denver at the AASLD The Liver Meeting congress, Genfit presented a detailed review of Nangibotide, its lead drug candidate in acute-on-chronic liver failure (ACLF). The efficacy signals highlighted come from studies conducted in other conditions: septic shock and severe COVID-19.
Efficacy signals obtained outside ACLF, including a targeted subgroup
The mechanism put forward by Genfit relies on TREM-1, an amplifier of inflammation. Nangibotide aims to “modulate this excessive amplification of the inflammatory response without directly impacting immune recognition mechanisms.” In ACLF, activation of this pathway has been observed as patients progress and has been associated with disease severity.
The candidate has been administered to 416 subjects, notably in three Phase 2 studies dedicated to septic shock and severe COVID-19. According to the company, its safety profile is overall comparable to that of placebo, with no safety signal identified.
In a subgroup of 118 patients with septic shock presenting high levels of soluble TREM-1, the SOFA organ failure score decreased by 2.5 points compared with placebo on day 5. The improvements in the respiratory, cardiovascular and renal components of this score are statistically significant.
Regarding 28-day mortality, the press release reports “favorable trends” in this subgroup. Among 219 patients with severe COVID-19, Nangibotide was associated with an improvement in clinical status and a reduction in 28-day mortality.
UPWARD: a placebo-controlled trial, efficacy as an exploratory endpoint
The randomized, placebo-controlled Phase 2a proof-of-concept study will enroll patients with grade 2 ACLF and a bacterial infection. They will be randomized in a 2:1 ratio between Nangibotide and placebo, administered as a continuous intravenous infusion for 3 to 7 days, in addition to standard of care.
The primary endpoint will be safety and the secondary endpoint pharmacokinetics, with efficacy signals falling under exploratory endpoints. Genfit plans to initiate the study by the end of 2026, subject to approvals from regulatory authorities, and expects first data in the second half of 2027.
For Jennifer C. Lai, hepatologist and professor at the University of California, San Francisco, the program “already benefits from solid clinical experience from Phase 2.” She added that the aim is “to determine whether the observed signals can translate into meaningful clinical benefit for these seriously ill patients.”
Among the risks listed, the company notably cites patient recruitment, the possibility that results may not support further development of Nangibotide, and potential safety signals in future studies.
