Comprehensive clinical and scientific data supporting Phase 2 development of nangibotide in ACLF unveiled to leading experts during AASLD The Liver Meeting®

Strong biological rationale in ACLF: TREM-1 modulation is designed to dampen excessive inflammatory amplification without directly targeting immune recognition

Prior Phase 2 clinical evidence demonstrated a well-characterized safety profile, efficacy signals in a subgroup of patients from septic shock trial, improved clinical status and lower mortality in patients with severe COVID-19

UPWARD Phase 2a proof-of-concept trial expected to be initiated by end of 2026, data expected second half of 2027 

GENFIT (Euronext: GNFT), a biopharmaceutical company dedicated to improving the lives of patients with rare and life-threatening liver diseases, yesterday unveiled an in-depth review of nangibotide, its new lead asset in acute-on-chronic liver failure (ACLF), during a scientific event gathering leading ACLF experts in Denver during AASLD The Liver Meeting®.

Professor Jennifer C. Lai, MD, MBA, Transplant Hepatologist, Endowed Professor of Liver Health & Transplantation, University of California, San Francisco (UCSF) commented: “The unmet need in ACLF remains tremendous, particularly for patients in the ICU who can rapidly progress to multi-organ failure. What is especially exciting about nangibotide is that we are not starting from scratch: the program already benefits from substantial Phase 2 clinical experience and proof-of-concept in acute inflammatory conditions characterized by organ dysfunction. This gives us a rare opportunity to bring an already extensively studied clinical-stage candidate into ACLF and explore whether those signals can translate into meaningful benefit for these critically ill patients.”

Strong biological rationale for TREM-1 modulation in ACLF
ACLF presents a major therapeutic challenge: controlling excessive systemic inflammation, a key driver of organ failure, without further compromising an already dysfunctional immune response. By modulating TREM-1, an amplifier of inflammation, nangibotide is designed to dampen excessive inflammatory amplification without directly targeting immune recognition itself.

This mechanism provides a strong biological rationale for nangibotide in ACLF, where TREM-1 pathway activation has been reported as patients progress from acute decompensation to acute-on-chronic liver failure, and has been associated with disease severity and adverse outcomes.

Prior Phase 2 clinical data highlight a favorable safety profile and encouraging efficacy signals
Nangibotide has generated substantial clinical experience across 416 exposed subjects, including three Phase 2 studies in septic shock and COVID-19, with an overall safety profile similar to placebo and no safety signal identified.

Efficacy signals were observed across both indications. In a subgroup of 118 septic shock patients with elevated levels of soluble TREM-1 (sTREM-1), nangibotide showed a 2.5-point greater reduction in SOFA¹ score versus placebo at Day 5, with statistically significant improvements in respiratory, cardiovascular and renal components, as well as favorable trends in Day 28 mortality and other clinical outcomes. In 219 patients with COVID-19, nangibotide was associated with improved clinical status and lower Day 28 mortality.

Together, this favorable safety profile and Phase 2 efficacy data provide clinical validation of the therapeutic rationale across acute inflammatory conditions characterized by organ dysfunction and support the development of nangibotide in ACLF, where systemic inflammation and multi-organ dysfunction are central features.

Advancing nangibotide into the UPWARD Phase 2 study in ACLF
The planned Phase 2a proof-of-concept trial is a placebo-controlled, randomized study designed to evaluate the safety of nangibotide in patients with ACLF grade 2 and a bacterial infection. Patients will be randomized to receive nangibotide or placebo (according to a 2:1 ratio), each administered as a continuous intravenous infusion for 3 to 7 days in addition to the standard of care. The primary endpoint of the trial is safety. The secondary endpoints will be pharmacokinetics. Exploratory endpoints will assess signals of efficacy.

The UPWARD trial is expected to initiate by the end of 2026, subject to regulatory approval, and initial data are expected in the second half of 2027.