Infectious Diseases | Immuno-OncologyRare Diseases | Autoimmune Disease

mRNA Based Treatments for Autoimmune Diseases

Scientific and technical advances enable our expansion into new therapeutic areas, the latest of which is autoimmune disease. Autoimmune diseases are defined by pathology resulting from an adaptive immune response against an antigen or antigens normally present within the body. There have been over 100 described autoimmune disorders; together these affect millions of patients worldwide. Moreover, in many cases disease is not well-controlled by existing treatment options and represent billions of dollars in healthcare costs. In healthy people, autoimmune reactions are prevented or controlled by mechanisms of self-tolerance. Lymphocytes (e.g., T and B cells) that are reactive against self-antigens are deleted during development, thus establishing central tolerance. Central tolerance is not completely protective, and so other mechanisms, collectively known as peripheral tolerance, act on any remaining self-reactive lymphocytes to control potential autoimmune pathology. These mechanisms of peripheral tolerance include induction of a reversible state of cellular non-responsiveness in self-reactive cells called anergy, and expression of inhibitory receptors or cytokines by other cells, such as dendritic cells, macrophages, and regulatory T cells (“Tregs”). The immune system works constantly to maintain balance between a state of immune activation and immune tolerance, sometimes called immune homeostasis.

We are developing several potential mRNA therapeutics that we believe have the potential to engage peripheral tolerance mechanisms to dampen autoimmune activation and help restore immune homeostasis. PD-L1 (mRNA-6981) is intended to induce the expression of this inhibitory receptor on myeloid cells, and IL-2 (mRNA-6231) is designed to preferentially increase the number of Tregs. We announced that IL-2 entered the clinic in August 2021, our first autoimmune therapeutic candidate to do so. It is also the first subcutaneously administered therapeutic program.