The Growing Potential of IL-6 Inhibition
Interleukin-6, or IL-6, is a key cytokine that drives immune and inflammatory diseases. Targeting the IL-6 pathway initially focused on autoimmune diseases such as rheumatoid arthritis, with the first IL-6 blocking therapy approved over 15 years ago. Today, IL-6 pathway inhibitors, antibodies targeting IL-6 or the IL-6 receptor, have been used worldwide to treat over a million patients with a variety of autoimmune and inflammatory conditions, including inflammation due to severe COVID-19 and inflammation that may occur from a type of cancer therapy (CAR T-cell).
The widespread and successful use of the IL-6 inhibitor class has led to a new wave of emerging insights paving the way for an IL-6 renaissance. Human genetic, epidemiological, and clinical trial evidence continue to implicate IL-6 as a key driver of disease.
We seek to utilize these emerging insights to expand the potential use of IL-6 inhibition in cardiovascular and autoimmune diseases.
Our Product Candidate
Our product candidate is pacibekitug, a long-acting, fully human, anti-IL-6 antibody with best-in-class potential and differentiated properties including a naturally long half-life, low immunogenicity and high binding affinity to IL-6. Excluding ongoing trials, pacibekitug was previously studied in approximately 450 participants, including patients with autoimmune disorders, across six completed clinical trials demonstrating deep inhibition of the IL-6 signaling pathway with relatively low amounts of drug, 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 use insights from various clinical trials 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)
If you’re a healthcare professional with questions about our science and/or you would like to be contacted by a Regional Medical Director, please email MedInfo@tourmalinebio.com.
