ABIONYX Pharma Announces Landmark Validation: A Study Published in NATURE Confirms Genetic Causality of Apolipoprotein A-I (ApoA-I) in Sepsis

A Global Turning Point for Critical Care Medicine

TOULOUSE, France & FULLERTON, Calif.--(BUSINESS WIRE)--ABIONYX Pharma, (FR0012616852 - ABNX - PEA PME eligible), a new generation biotech company dedicated to the world's only recombinant apoA-I, today announced the publication of a ground breaking study in Scientific Reports in Nature Portfolio titled “Plasma apolipoprotein A-I is a causal protective factor in sepsis.” (https://www.nature.com/articles/s41598-025-19204-2#auth-Keith_R_-Walley-Aff1)

This landmark publication provides, for the first time, genetic proof of a causal linkage between higher plasma ApoA-I levels and a lower incidence of sepsis and lower mortality in patients who do develop sepsis. At the same time, the publication provides genetic validation of the well-studied mechanism of apoA-I’s beneficial impact on sepsis – the sequestration of the bacterial lipid toxin, LPS, which is responsible for the manifestations of sepsis. The report provides evidence that apoA-I is also effective in reducing mortality in Gram positive sepsis driven by the bacterial toxin lipoteichoic acid. Importantly, the findings were replicated across three independent data sets, including both Caucasian and Asian sepsis sufferers. The structural protein which defines HDL is apoA-I.

The study analyzed 442,601 participants from the UK Biobank, including 11,643 sepsis cases, and validated the findings across two large international cohorts. Results demonstrate that each standard deviation increase in plasma apoA-I levels reduces the incidence of sepsis by 13% and 28-day mortality by 27%.

Using Mendelian randomization, the researchers confirmed that this protective effect is causal and independent of other lipid fractions (HDL-C, LDL-C, triglycerides).

Mechanistically, higher apoA-I levels were linked to a reduction in circulating endotoxin (LPS) levels, reinforcing apoA-I’s role as a central modulator of inflammatory response and innate immunity in sepsis.

“This publication is a game-changer,” said Dr. Rob SCOTT, MD, Head of R&D and CMO of ABIONYX Pharma. “For decades, the field of sepsis has searched for a causal target. The mechanistic effect of apoA-I and HDL has been well documented over the last 40 years but now, this new genetic validation provides proof that apoA-I is a major factor determining whether patients develop sepsis and whether they survive it.

This major publication in Nature is a significant milestone that reinforces the scientific and strategic value of the company in ongoing discussions with a leading partner in sepsis.