GENFIT Highlights ACLF Development Strategy at “ACLF Day” during AASLD The Liver Meeting 2023 - Seite 2

ACLF: high short-term mortality, no approved treatment

ACLF is a serious, but potentially reversible, condition in patients with chronic liver disease and cirrhosis, which is associated with multiple organ failure, and a 23% to 74% mortality at 28 days⁶ depending on grade severity. As part of the “ACLF Day” event during AASLD, the critical need for treatment has been highlighted by leading experts in ACLF.

Dr Jennifer C. Lai, MD, MBA, Transplant Hepatologist, Endowed Professor of Liver Health & Transplantation, University of California, San Francisco (UCSF) said: “ACLF is a terrifying condition for patients and their caregivers, but it’s equally terrifying for clinicians, because we know our patients are in grave and immediate danger, and we have no approved treatment to help them. It is very frustrating and therefore it is critical that therapies are developed, ideally to reverse the course of the disease or at least to give the patient more time to get a potentially life-saving transplantation. This is an area of huge unmet medical need and I welcome new efforts to develop potentially helpful therapies.”

GENFIT’s pipeline in ACLF: targeted to address the unmet need

GENFIT’s ACLF therapeutic candidates have been strategically selected based on the pathophysiology of ACLF – as defined by liver experts and consortiums such as EF-CLIF (European Foundation for the study of Chronic Liver Failure) – to address the most relevant pathways. Considerations about the limitations in current standard of care have also been taken into account. Among the pathways identified, priority is given to systemic inflammation, cell death and microbiota.

Dean Hum, PhD, Chief Scientific Officer of GENFIT, commented: “Our R&D strategy is centered on understanding the pathophysiology of ACLF and selecting molecules that we believe are best positioned to impact specific relevant pathways. This multi-factorial approach will allow us greater chances of success as well as leveraging potential synergies via combinations. It also offers the possibility to apply key learnings across all ACLF programs, to accelerate overall execution.”

The ACLF pipeline overview:

• VS-01 – Phase 2 initiated (interim data readout targeted for the end of 2Q24): VS-01 is a liposomal-based technology designed to remove ammonia and other ACLF toxins from the blood (peritoneal route of administration)
• NTZ – Reformulation and Phase 2 under preparation (proof-of-concept study initiation targeted for the first half of 2025): NTZ is an anti-inflammatory and anti-bacterial agent aiming to reduce systemic inflammation, and impede release of PAMPs⁷ and bacterial translocation (oral route of administration)
• SRT-015 – First-in-Human study under preparation (expected to be initiated 2H24): SRT-015 is an ASK1 inhibitor, liver-centric, aimed at inhibiting cell death, inflammation and fibrosis (injectable route of administration)
• CLM-022 – Preclinical proof of concept under preparation (expected to start 2024): CLM-022 is an NLRP3 inflammasome inhibitor aimed at inhibiting systemic inflammation and cell death (pyroptosis)
• VS-02-HE – Completion of IND enabling studies expected in 2025: VS-02-HE aims at reducing hyperammonemia, stabilizing blood ammonia and preventing hepatic encephalopathy (oral route of administration)