IL-18BP Fusion Protein - Evommune
Treating chronic inflammatory disease through IL-18 inhibition.
IL-18BP Fusion Protein
Interleukin 18 (IL-18) is a pro-inflammatory cytokine of the IL-1 family that as a general amplifier of inflammation, capable of driving multiple inflammatory responses, including Th1, Th2, Th17/22 and innate pathways, all of which are highly implicated in AD. Broadly impacting these pathways is crucial for treating conditions with heterogeneous inflammation, where targeting a single pathway may not be optimal. When the IL-18 pathway is upregulated in a chronic, cyclical fashion, it can trigger a cascade of inflammatory mediators that ultimately lead to tissue damage and disease manifestations, including those we see in atopic dermatitis. IL-18 also directly disrupts essential skin barrier functions, positioning it as a pivotal pathogenic factor. Targeting IL-18 offers broader therapeutic utility with a novel approach, simultaneously reducing inflammation and restoring tissue integrity for patients with complex inflammatory conditions.
IL-18 binding protein (IL-18BP) is a naturally occurring inhibitor of IL-18. EVO301 is an anti-serum albumin Fab-associated (SAFA) IL-18BP fusion protein designed to neutralize aberrantly upregulated IL-18 activity, which is seen in various inflammatory and autoimmune diseases.
Targeting IL-18 with a smaller, anti-serum albumin-binding IL-18BP fusion protein has the potential to treat many inflammatory diseases by inhibiting IL-18’s pro-inflammatory activity. Using native human IL-18BP reduces immunogenic potential compared to traditional monoclonal antibodies. Additionally, the anti-serum albumin-binding fusion protein may allow more effective distribution to inflamed tissues than normal, larger sized monoclonal antibodies.
Our randomized, double-blind, placebo-controlled Phase 2a trial was completed in February 2026 and met its primary endpoint, generating data that demonstrated highly statistically significant and clinical meaningful activity in moderate-to-severe atopic dermatitis. This activity with an IL-18 targeting therapy supports the relevance of this pathway in disease pathophysiology and reinforces that pathways beyond classic Th2 biology can contribute meaningfully to disease activity. We are advancing EVO301 into a Phase 2b dose‑ranging trial in patients with AD, using a subcutaneous formulation of EVO301.
Elevated IL-18 cytokine expression is associated with the pathogenesis of multiple inflammatory diseases.
Preclinical and translational studies have demonstrated clear rationale for targeting IL-18, in both AD and in inflammatory bowel diseases (IBD). Gene variants in the IL-18 pathway are associated with the risk of developing AD and IBD. Furthermore, increased levels of IL-18 have been found in AD and IBD patients, correlating with disease severity. In translational studies, IL-18 has been shown to drive key pathological processes in each disease through amplification of inflammation and barrier disruption. IL-18 inhibition via anti-serum albumin-binding IL-18BP is currently being evaluated in:
- Atopic Dermatitis: Atopic Dermatitis is a chronic inflammatory skin disorder that affects approximately 15-20% of children and 1-3% of adults, approximately 40% of which have a moderate-to-severe form of the disease. Atopic dermatitis, which expresses elevated levels of IL-18, is characterized by abnormalities in immune regulation and skin barrier function. The disease typically manifests with itchy eczematous skin lesions. The disease has a significant impact on the patients’ quality of life including sleep, self-esteem, interpersonal relationships, and participation in school or work.
- Ulcerative Colitis: Ulcerative colitis is a chronic inflammatory bowel disease that primarily affects the colon and rectum. It is estimated to impact approximately 1 million people in the United States, with varying degrees of severity. The disease is characterized by persistent inflammation and ulceration of the colon’s inner lining, leading to symptoms including abdominal pain and diarrhea, often accompanied with blood or mucus. Ulcerative colitis is associated with immune system dysregulation and disruptions in the gut microbiome. The condition significantly affects patients’ quality of life, often causing fatigue, emotional distress, and limitations in daily activities, including work, school, and social interactions.
- Other Indications: We believe EVO301 has the potential to address several additional chronic inflammatory diseases in which dysregulation of the IL-18 pathway contributes to chronic inflammation and tissue damage driving disease pathology, including certain cardiovascular-related inflammatory conditions and food allergies.