IL-6 Renaissance
Interleukin-6, or IL-6, is a keystone cytokine which drives immune and inflammatory diseases. Targeting IL-6 to treat autoimmune diseases initially focused on rheumatologic conditions such as rheumatoid arthritis. Today, the anti-IL-6 and anti-IL-6 receptor (IL-6R) antibody class has over two decades of clinical experience, treating over a million patients with a variety of autoimmune and inflammatory diseases.
The widespread and successful use of the IL-6 class has led to a new wave of emerging insights paving the way for an IL-6 renaissance. Sustained academic and investigator enthusiasm for IL-6 inhibition has driven successful off-label use in a wide-range of immune and inflammatory diseases. Additionally, continually-emerging human genetic, biomarker, and epidemiologic translational data further implicate IL-6 as a key driver of disease.
This IL-6 renaissance is a significant opportunity to reshape the treatment of immune and inflammatory diseases. We seek to utilize these emerging insights and formally validate the therapeutic potential of IL-6 inhibition.
Our Product Candidate
Our product candidate is pacibekitug (also referred to as TOUR006), a long-acting anti-IL-6 antibody that exhibits best-in-class properties including a high binding affinity to IL-6 and a long half-life. Pacibekitug has been studied in hundreds of autoimmune patients demonstrating deep inhibition of the IL-6 signaling pathway with relatively low amounts of drug exposure and delivery in an infrequently administered, low-volume, subcutaneous administration.
Our strategy is to develop pacibekitug in indications where IL-6 pathway inhibitors have been underexplored despite compelling signals of clinical activity. We seek to leverage published observations of IL-6 pathway inhibitors in various diseases as well as insights from clinical trials of competitor IL-6 pathway inhibitor programs to maximize the therapeutic potential of pacibekitug. The extensive clinical experience with pacibekitug to date allows us to move directly into late-stage/pivotal programs to rapidly deliver pacibekitug to patients.
IL-6 Mechanism of Action
IL-6 is a pleiotropic cytokine which plays a key role in driving inflammation and cellular and humoral immune responses. In typical immunity, IL-6 is produced by various immune cells, including monocytes, macrophages, T cells, and B cells as well as fibroblasts and other non-immune cells, in response to cellular stresses and proinflammatory signals. Increased levels of IL-6 induce the acute phase inflammatory response, activating the innate immune system and providing a nonspecific response to infections and pathogens.
In autoantibody-mediated diseases
IL-6 plays a key upstream role in autoantibody-mediated diseases. IL-6 acts as a promotion factor for B-cell and plasma cell survival, promoting autoantibody production. In addition, IL-6 serves as a key differentiating factor for T-cells, specifically promoting the development of pathogenic Th17 cells and T follicular helper (Tfh) cells which, in turn, further promote B cell proliferation and autoantibody production. Importantly, IL-6’s role in acute phase proinflammatory signaling may also distinctly drive aspects of disease pathogenesis.
IL-6 mediated impacts of B and T cell pathways*
*Adapted from Cabezas et al., Front. Immunol. (2022)
