Genfit plans Phase 2 liver failure trial after acquiring immunomodulator from Inotrem

Why it matters: Focused on ACLF, Genfit has built a pipeline led by the G1090N, which delivered Phase 1 data in January, and featuring multiple preclinical programs. The pipeline positions Genfit to treat various aspects of ACLF but, with the biotech ending a Phase 2 program last year over a safety signal, all the drug candidates are in early development.

• Buying nangibotide gives Genfit a Phase 2-ready asset. Inotrem ran Phase 2 trials that tested the inhibitor of triggering receptor expressed on myeloid cells-1 (TREM-1) in more than 400 people with acute inflammatory conditions.
• Genfit has yet to disclose the financial details of the deal, and Inotrem investor Sofinnova did not immediately respond to a request for information. 

How it works: When turned on, TREM-1 triggers a heavy release of inflammatory cytokines (via the NF-κB pathway). In conditions like septic shock, this pathway goes into overdrive, causing widespread tissue damage, endothelial failure, and organ shutdown. Nangibotide works by selectively inhibiting the TREM-1 receptor.

Backstory: Paris-based Inotrem emerged in 2014 with €18 million from a Series A round co-led by Edmond de Rothschild Investment Partners and Sofinnova Partners. Ten years later, the biotech said that it had reached agreement with the FDA for a Phase 3 trial of nangibotide in septic shock.

• Inotrem raised €58 million of equity and debt in 2020 and secured €45 million in public funding in 2021 as it tested nangibotide in COVID-19 patients. 
• However, U.S. study registry ClinicalTrials.gov never published a listing for the proposed Phase 3 trial and the biotech’s website went offline this year.

Zoom in: The foundations established by Inotrem position Genfit to start a Phase 2a proof-of-concept trial in the fourth quarter and aim to report data from the trial next year. Genfit will leverage the safety database, manufacturing platform and regulatory packages that Inotrem developed for nangibotide to accelerate development in ACLF.

Yes, but: Inotrem never ran a clinical trial in ACLF. The biotech focused on septic shock, with an interlude during the pandemic in which it explored nangibotide’s effect on people with severe COVID-19.

• Genfit cited a post hoc analysis of Phase 2 trials in septic shock and COVID-19 as evidence of the drug candidate’s potential. Nangibotide showed multiple efficacy signals, including a statistically significant reduction in mortality, Genfit said.

Bottom line: The deal provides Genfit with a quick and, while financial details remain private, potentially relatively affordable path back into Phase 2 development in ACLF.