Lassen’s lead program targets the IL-11 pathway, applying novel science against a new mechanism of action to potentially treat inflammatory fibrotic diseases and oncology.
The Il-11 Pathway
- IL-11 is a member of the IL-6 family of cytokines which play prominent roles in chronic inflammation, autoimmunity and cancer
IL-11 binds to IL-11R and forms a complex with gp130, resulting in functional cell signaling through the STAT3 or ERK pathways.
IL-11 plays a critical role in the initiation and maintenance of chronic fibrotic responses and as a result, blocking this pathway represents a promising approach for both chronic fibrotic/inflammatory diseases and multiple tumor types.
IL-11 in Fibrosis
IL-11 is a major driver and central mediator of fibrosis
- Local overexpression of IL-11 leads to local fibrosis
- Differentiation of fibroblasts into activated myofibroblasts is a defining feature of fibrosis and IL-11 is the most highly upregulated gene during this transition
- IL-11 receptor is highly expressed in fibrotic disease
- IL-11 production is elicited by the major known pro-fibrotic factors including TGFβ, FGF, PDGF, CTGF and IL-13
- IL-11 expression is elevated in patients with systemic sclerosis and idiopathic pulmonary fibrosis
IL-11 in CANCER
IL-11 and other components of the IL-11 pathway are overexpressed in a number of cancer types. In addition, cancer-associated fibroblasts play an important role in the tumor microenvironment where IL-11 appears to be an important mediator between tumor and stromal cells. This leads to IL-11 affecting proliferation, angiogenesis and metastasis, while simultaneously inducing resistance of tumors to existing therapies including chemotherapy and immunotherapy. Blocking this pathway has emerged as an exciting therapeutic approach for tumor therapeutic development.
The concept of combating tumor progression through inhibition of growth-promoting cytokines like IL-11 is emerging as a therapeutic opportunity that bypasses the difficulties of targeting intracellular signaling molecules and transcription factors.