Clinical Development


AB2 Bio has developed the first and proprietary assay to detect and measure free IL-18 in body fluids, which gives us the capability of identifying diseases associated with free IL-18 levels. The assay could also be used as a companion diagnostic to select patients most likely to respond to treatment with IL-18BP.


AB2 Bio is pioneering an empirical therapeutic approach to a rational selection of medical targets. If patients with high levels of free IL-18 can be identified, the clinical impact of treatment with IL-18BP will be maximized, while those patients unlikely to respond will not be unnecessarily exposed to ineffective medicines. Such an approach will reduce regulatory hurdles and increase the chances of successful clinical trials.


Extensive Phase I, Ib and II clinical trial results demonstrated that recombinant human IL-18BP is very well tolerated and has an excellent safety profile.

Primary HLH

People with HLH usually develop symptoms within the first months or years of life. Symptoms may include fever, enlarged liver or spleen, cytopenia (decreased number of blood cells), and neurological abnormalities. All forms of HLH, including cases treated adequately, may have a high mortality rate. The long-term outlook (prognosis) of familial forms without treatment is poor, with a median survival of less than 2 months to 6 months after diagnosis. These disorders can be either inherited (familial or primary) or secondary to other conditions (rheumatic diseases, cancer or infections) such as Macrophage Activation Syndrome (MAS), a severe complication of rheumatic diseases. NLRC4 mutation and XIAP deficiency can be considered part of primary HLH.


AB2 Bio is currently conducting a pivotal Phase III clinical trial in patients (children and adults) with IL-18 driven monogenic autoinflammatory conditions: NLRC4 mutation and XIAP deficiency. For further information, click here or click here.


NLRC4 mutations. The normal function of the NOD-like receptor C-4 (NLRC4) protein is to detect infections and activate the innate immune system to combat these infections. Gain-of-function mutations in the NLRC4 gene (NLRC4 mutations) have been identified in patients suffering from life threatening systemic inflammation. The continuous and permanent activation of the protein leads to the unnecessary production of IL-18 and to the inability of endogenous IL-18BP to block IL-18 thus resulting in extremely high levels of circulating free IL-18 through the body. In the cases that have been reported, this causes two predominant clinical phenotypes: MAS and/or enterocolitis. The enterocolitis is likely to be a result of the expression of the NLRC4 protein in the gut mucosa where NLRC4 is the main inflammasome present and IL-18 the main effector cytokine.


XIAP deficiency. XIAP deficiency is associated with high levels of IL-18 and free IL-18. One of the functions of the X-linked inhibitor of apoptosis protein (XIAP) is to inhibit the activity of NLRC4. Therefore, a deficiency in XIAP function (loss of function) will result in the same pathophysiology as that seen with a gain in function of the NLRC4 protein. Indeed, XIAP deficiency share many pathological similarities with NLRC4 patients, particularly with respect to MAS  and enterocolitis.

Secondary HLH

Macrophage Activation Syndrome. Macrophage Activation Sysdrome (MAS) is a very severe complication of rheumatic diseases. Mortality ranges between 10-30% for patients with MAS and there is no registered therapy. MAS occurs frequently in systemic Juvenile Idiopathic Arthritis (soJIA) and in Adult onset Still’s Disease (AOSD) patients. It is characterized by severe systemic inflammation with pancytopenia, liver insufficiency, coagulopathy and neurological symptoms. The underlying cellular mechanism is the uncontrolled activation and proliferation of T lymphocytes and macrophages leading to a cytokine storm with a predominant role of IL-18.

Adult onset Still's Disease

Adult onset Still’s Disease (AoSD) is a rare orphan inflammatory disorder typically associated with episodes of high spiking fevers, inflammatory synovitis, arthralgia and a general severe malaise. The clinical severity of AoSD is associated with laboratory markers of systemic inflammation, where high IL-18 levels are a dominant and constant feature during disease activity.


The Phase II clinical trial in Switzerland, France and Germany has been completed. For further information, click here.

Other Indications

The combination of AB2 Bio’s assay and drug favors a personalized medicine approach to treat severe and life threatening diseases and build a strong pipeline with high chances of clinical success.

Using AB2 Bio’s proprietary assay, a thorough evaluation of other severe inflammatory diseases is ongoing to determine whether other diseases driven by high levels of free IL-18 can be identified. If positive, AB2 Bio will consider further clinical development.