Our Science

Our initial product candidate, itolizumab, is a first-in-class immune-modifying monoclonal antibody that targets the CD6-ALCAM signaling pathway. The CD6-ALCAM signaling pathway plays a central role in the modulation of effector T cells (Teff cells). Activated Teff cells drive a number of immuno-inflammatory diseases across therapeutic areas including transplant science, systemic autoimmunity, pulmonary, neurologic, gastrointestinal, renal, vascular, ophthalmic and dermatologic disorders. Therefore, we believe itolizumab may have broad therapeutic utility in treating a large and diverse set of severe immuno-inflammatory diseases.

Autoimmunity Is a Balancing Act

The role of the immune system is to defend the body against foreign organisms and cells, and in doing so it must distinguish accurately between self and non-self entities, a process called tolerance. Autoimmunity is an immune response directed against the body’s own healthy cells and tissues, and is the underlying process in many inflammatory diseases. Autoimmunity results from a loss of tolerance caused in part by an imbalance in the relationship between Teff cells and regulatory T cells (Treg cells).

Stephen Connelly, Ph.D., Equillium’s Chief Scientific Officer, discusses the role of T cells in modulating immune responses

The CD6-ALCAM Pathway Plays a Central Role in Autoimmunity

CD6 is a co-stimulatory receptor that uniquely modulates T cell activity and trafficking and is a key checkpoint in regulating Teff cells that are central to autoimmune responses. Activated leukocyte cell adhesion molecule (ALCAM) is a ligand of CD6 that is expressed on hematopoietic tissues such as antigen-presenting cells, where it is important for immune synapse formation and optimal co-stimulation. Binding of ALCAM to CD6 leads to the downstream activation of several mitogen activated protein kinase (MAPK) pathways related to T cell activation, proliferation, differentiation and survival. Preclinical and clinical studies have shown that blockade of the CD6-ALCAM pathway leads to selective inhibition of pathogenic Teff cell activity and trafficking, while preserving the important regulatory function of Treg cells, which provide ongoing immune surveillance.

Stephen Connelly, Ph.D., Equillium’s Chief Scientific Officer, discusses the role the CD6-ALCAM pathway plays in the activity and trafficking of Teff cells

CD6-ALCAM Pathway Central to Immuno-inflammation

Itolizumab Inhibits Pathogenic T Cell Activity & Trafficking

Itolizumab

Itolizumab is a clinical-stage, first-in-class immune-modifying monoclonal antibody that targets the CD6-ALCAM signaling pathway to selectively downregulate pathogenic Teff  while preserving Treg cells critical for maintaining a balanced immune response. Equillium is developing itolizumab for conditions where there are limited to no treatment options, including acute graft-versus-host disease, uncontrolled moderate to severe asthma and lupus nephritis.

In preclinical studies, blockade of CD6 with itolizumab led to a reduction in Teff cell proliferation and downregulation of several important pathways that contribute to Teff cell development. The downregulation of these pathways is accompanied by decreased secretion of the pro-inflammatory Teff cytokines IFN-γ, TNF-α, IL-6 and IL-17. Additionally, inhibiting the binding of ALCAM to CD6 modulates lymphocyte trafficking and results in reduced Teff cell infiltration into inflamed tissues.

Krishna Polu, M.D., Equillium’s Chief Medical Officer, discusses how itolizumab uniquely modulates both the activity and trafficking of teff cells.