Lassen’s lead program targets the IL-11 pathway, applying novel science against a new mechanism of action to potentially treat fibro-inflammatory diseases such as thyroid eye disease (TED) and idiopathic pulmonary fibrosis (IPF).
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.
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 thyroid eye disease and idiopathic pulmonary fibrosis
IL-11 in Thyroid Eye Disease
Thyroid eye disease (TED) is an autoimmune condition that affects the eye muscles, eyelids, and other tissues surrounding the eye. It is often associated with Graves’ disease, a condition where the immune system attacks the thyroid gland, causing it to produce excessive amounts of thyroid hormone.
Recently emerging research suggest that IL-11 may play an important role in the development and progression of TED. IL-11 is overexpressed in the blood and orbital tissue of patients with TED, implicating IL-11 in disease pathobiology.
Additionally, in TED patient-derived orbital fibroblasts in vitro, IL-11 has been shown to significantly induce pathological effects fundamental to TED biology, which can be blocked effectively by LASN01, an anti-IL11R antibody per data generated at Lassen. The data suggests that blocking IL-11R signaling may be a promising, novel therapeutic approach for the treatment of TED.