Technology Networksrecently had the pleasureof speaking with Bruce Steel, CEOEquillium, Inc. to learn more about how they are leveraging their comprehensive understanding of immunobiology to develop novel treatments for inflammatory and autoimmune disorders.Bruce provides insight on the various indications the company is currently developing treatments for, elaborates on the clinical progress of their initial product candidate EQ001 (itolizumab), and explains the role CD6 plays in autoimmunity and how it can be targeted therapeutically.

Laura Lansdowne (LL): How can immunobiology be harnessed to develop therapeutics?Bruce Steel (BS): The role of the immune system is to defend the body against foreign organisms and cells, including cancerous 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 bodys 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 effector T cells and regulatory T cells. Therefore, developing therapeutics, such as EQ001 (itolizumab), that target these critical regulators of immune activation pathways has the potential dramatically improve the lives of patients with severe autoimmune and inflammatory disorders.LL: What indications are you currently developing treatments for?BS: We select target indications based on three primary criteria: strong scientific rationale for why itolizumab has potential to be a best-in-class therapeutic approach, areas of high unmet medical need where there are little or no treatments available today, and indications where we believe there is an attractive future commercial opportunity. Today we have ongoing clinical trials with itolizumab in acute graft-versus-host disease (GVHD), uncontrolled asthma and lupus/lupus nephritis.

While these three indications are our initial areas of focus, we believe itolizumab has the potential to be developed in other areas such as transplant science, systemic autoimmunity, pulmonary, neurologic, gastrointestinal, renal, vascular, ophthalmic and dermatologic disorders.We licensed itolizumab from our partner Biocon Limited who developed the drug and received regulatory approval in India for the treatment of psoriasis.LL: Can you tell us more about the mechanism of your drug candidate EQ001 (itolizumab)?BS: Itolizumab is a clinical-stage, first-in-class monoclonal antibody that selectively targets the CD6-ALCAM pathway, which plays a central role in modulating the activity and trafficking of effector T cells that drive a number of immune-inflammatory diseases.LL: What role does CD6 play in autoimmunity?BS: CD6 is a novel co-stimulatory receptor that uniquely modulates T cell activity and trafficking. It is a key checkpoint in regulating effector T cells that are central to autoimmune responses. CD6 binds activated leukocyte cell adhesion molecule (ALCAM). ALCAM is expressed on both antigen-presenting cells and tissue including the skin, gut, lung and kidney.In preclinical studies, blockade of CD6 with itolizumab leads to reduction in effector T cell activation and proliferation. Additionally, inhibiting the binding of ALCAM to CD6 with itolizumab modulates lymphocyte trafficking and reduces effector T cell infiltration into inflamed tissues.

Our work with CD6 builds upon the research conducted from researchers at the Dana-Farber Cancer Institute, our partner Biocon, and other leading academic centers. Today there are numerous peer reviewed publications related to the novel CD6 checkpoint receptor and targeting the CD6-ALCAM pathway.LL: Can you elaborate on the clinical progress of itolizumab?BS: Itolizumab is currently being studied in three different indications: acute graft-versus-host disease (aGVHD), uncontrolled moderate to severe asthma and lupus/lupus nephritis. This is an important catalyst year for Equillium as we expect initial data from all three programs in 2H 2020.

Each of these studies will allow us to understand the safety of itolizumab in these different disease areas and understand what potential dose we will carry forward. This is important as we consider making a larger investment in Phase II studies to advance the program.Bruce Steel was speaking with Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.

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Exploiting Immunobiology To Treat Severe Autoimmune and Inflammatory Disorders - Technology Networks