AVTX-007 is a fully human anti-interleukin (IL)-18 monoclonal antibody with the potential to address multiple immune-mediated diseases, including Still’s disease and certain cancers like relapsed or refractory multiple myeloma.

Targeting IL-18

IL-18 is a proinflammatory cytokine with pleiotropic and immunoregulatory effects. IL-18 is characterized by its ability to induce production of interferon-gamma (IFN-g) and other inflammatory cytokines from natural killer (NK) and T helper 1 (Th1) cells in synergy with IL-12. It has been shown to play a critical role in various autoinflammatory diseases, such as Still’s disease, as well as in the inflammation and immunosuppression associated with multiple myeloma.

Still’s disease is a rare systemic inflammatory disorder of unknown cause. Affected individuals may develop episodes of high, spiking fevers, a pink or salmon colored rash, joint pain, muscle pain, sore throat, and other symptoms associated with systemic inflammatory disease.

Elevated levels of IL-18 have been shown to be correlated with disease activity in patients with active Still’s disease.

Serum IL-18 Significantly Elevated in AOSD

Multiple myeloma is a cancer that forms in plasma cells. Cancerous plasma cells accumulate in the bone marrow, compromising the body's ability to produce antibodies that fight infection.  IL-18 is essential for liquid tumor growth, survival, and metastasis, as well as local immunosuppression. Targeting IL-18 can increase tumor immune cell access by inhibiting tumor-induced immune suppression.

IL-18 and the Tumor Microenvironment 

Elevated levels of IL-18 have been shown to be correlated with significantly worse median survival (42 mo vs >84 mo; P=0.0026; HR, 1.84) in patients with multiple myeloma. Reducing IL-18 levels has been shown to prolong survival in rodent models.

Elevated IL-18 Correlated With Poor Survival

Attributes of AVTX-007

  • Fully human, high-affinity, neutralizing monoclonal antibody against IL-18
  • Generally well tolerated up to 1000 mg in phase 1 and 1b clinical studies
  • Potential for companion diagnostic with a biomarker-driven clinical development approach