Our Focus

Delinia is a biotechnology company developing novel therapeutics for the treatment of autoimmune diseases. Delinia’s lead program is a molecule that potentiates and expands Regulatory T Cells (Tregs), powerful immune cells that are critical to maintaining self-tolerance and immune system homeostasis. Tregs are critically important immune regulatory cells in the pathophysiology of cancer and autoimmune disease.

Autoimmune Disease

Autoimmune Disease is caused by the human immune system misidentifying the body’s own cells and tissues as foreign, resulting in immune attack on those cells and tissues and disease pathology. Autoimmune Diseases are at their core the result of a failure of the immune system to distinguish self from non-self.

Autoimmune Diseases include Systemic Lupus Erythematosus, Systemic Sclerosis, Sjorgren’s Syndrome, Multiple Sclerosis, Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Autoimmune Myopathies, Myasthenia Gravis, Type 1 Diabetes, Crohn’s Disease, Pemphigus Vulgaris, Vitiligo, and Alopecia Areata, among others. These diseases often strike in the prime of life, resulting in decades of disease and disability. Current therapy is primarily based on the use of highly immunosuppressive drugs, which are only partially effective and carry risks of short-term and long-term toxicities and side effects. There is a great need for new and effective treatments for Autoimmune Diseases.

Restoring Balance to the Immune System

Immune system homeostasis is maintained by a balance between different immune cell types, notably Effector T Cells and Regulatory T Cells (Treg).  Proper maintenance and regulation of this balance enables the immune system to mobilize to fight off foreign infectious agents while at the same time maintain tolerance to self-antigens.

Immune Tolerance is the result of two immunological mechanisms: Central Tolerance and Peripheral Tolerance.  Central Tolerance is characterized by the “education” of developing T cells in the thymus, in which T cells directed to self-antigens are eliminated before being released into the circulation.  Peripheral Tolerance is a mechanism in which self-reactive T cells that have circumvented Central Tolerance mechanisms are actively suppressed by Tregs, a relatively small subset of T cells.  Tregs maintain self-tolerance, and are also generated during the natural history of all immune responses to foreign antigens as a means of self-limiting immune responses.

The central role of Tregs in autoimmune disease is demonstrated in the human disease IPEX (Immunodysregulation Polyendocrinopathy Enteropathy X-linked) Syndrome, a devastating disease in which there is a genetic deficiency in the generation of functional Tregs.  Infants with IPEX Syndrome develop a rapid and fatal multi-organ autoimmune disease.  Furthermore, experimental studies in mice have shown that deletion of Tregs in adult animals similarly results in the rapid development of autoimmune disease.  Finally, there are many studies in the scientific literature that have reported a relative deficiency of Treg numbers and/or function in a number of autoimmune diseases.

Modulating Regulatory T Cells

There is strong clinical evidence that augmenting Tregs as a means of restoring immune system balance can benefit patients with autoimmune diseases.  Early stage clinical trials in several diseases in which patients are infused with autologous Tregs have shown significant signs of efficacy.  Several clinical trials in which patients have been treated with low-dose IL-2, a key Treg growth factor, have demonstrated augmentation of Treg levels and significant signs of efficacy.

Tregs are a relatively small population of T Cells, representing approximately 5% of CD4+ T cells in human blood.  The IL-2 pathway is key to the production and function of Tregs.  Treg production and function are regulated in a distinct manner from CD4+ T Effector cells and CD8+ T cells.  Effector T cells are activated by IL-2, and produce their own IL-2 in a “feed-forward” form of activation.  Tregs do not produce their own IL-2, and are dependent on IL-2 from other immune cells.  Thus, Tregs have a close interaction with and dependency on the immune cells that they regulate.

The majority of Effector T cells express a form of the IL-2 Receptor called the “intermediate affinity” IL-2 Receptor (IL2Rβγ), while activated Effector T cells transiently express the “high affinity” IL-2 Receptor (IL2Rαβγ).  In contrast, Tregs express the IL2Rαβγ constitutively and at high levels.  Low-dose IL2 therapy attempts to selectively target Tregs by taking advantage of the difference in affinity between the IL2βγ and the IL2αβγ receptors.  However, the ability to distinguish between these receptors by lowering the dose of IL-2 is imperfect, results in significant toxicity, and because of its short circulating half-life, requires daily administration.


Delinia’s Novel Therapeutic

Delinia has developed a novel protein therapeutic that is a potent, highly selective agonist of the IL-2 Receptor on Tregs.  This molecule activates and augments the levels of a cell type that is the natural regulator of multiple arms of the immune response, in contrast with immunosuppressive drugs that can cause profound immunosuppression and both short- and long-term toxicities.  Our data indicate that this molecule will be a new paradigm in the treatment of autoimmune disease.

Delinia’s Novel Therapeutic