Immune Regulation

Enabling Immune Regulation

Many pathological conditions stem from deregulation of the immune system. Enzo has developed proprietary technology in two areas of immune regulation: Oral tolerance and Immune modulation.

Oral tolerance

An essential property of the immune system is its ability to distinguish between “self” and “non-self”‘, or foreign entities. In a healthy organism, self-entities are not attacked, whereas foreign entities may or may not be attacked, depending on a complex series of “clues” that indicate the potential harm of that entity. Under certain conditions a host organism ceases to recognize one of its own entities, or antigens, as “self” and initiates an immune response directed against that “self “antigen resulting in an autoimmune condition. Examples of autoimmune diseases are rheumatic heart disease, where an autoimmune response is directed against heart tissue, and Crohn’s disease, where the response is directed at intestinal cells.

Oral administration of the same or similar antigens that are responsible for the autoimmune response can induce tolerance and result in deregulation of the immune system, thereby diminishing the undesirable immune response. The induction of this oral tolerance is mediated by the cells of the intestinal mucosa that act to induce to induce oral tolerance to the offending antigen by the same process that they utilize to induce tolerance to the numerous foreign antigens in the food that we consume.

Based on this platform, we have developed therapeutic modalities and conducted clinical trials for a variety of autoimmune diseases including Crohn’s disease, autoimmune uveitis and hepatitis.

Immune modulation

Mounting an immune response can proceed through two main immunological response mechanisms: antibody-based and cell-based responses. In some cases an immune disorder can be corrected by changing the modality of the response from antibody-based to cell-based or from cell-based to antibody-based. We have discovered and developed a number of small molecules that can redirect the immunological response in a beneficial way. We have shown that these small molecules, glycosylceramides, can act to ameliorate a number of immune disorders in animal models of colitis, metabolic syndrome, bone marrow transplantation, hepatitis and hepatocarcinoma. We have studied these compounds in clinical trials of individuals with metabolic syndrome.

Alequel ™

Alequel ™, based on Enzo’s proprietary immune regulation technology platform, is a unique investigational drug that is designed to harness the patient’s own immune system to alleviate the symptoms of Crohn’s disease. This therapeutic application of immune tolerance offers a new approach for a disease with few current treatment options. Alequel™, by reducing inflammation resulting from the autoimmune response, reduces the patient’s dependence on systemic immunosuppressant drugs that often have undesirable side effects. In both animal model systems and in human clinical trials Alequel ™ has been shown to be a safe and potentially effective treatment for patients with Crohn’s Disease.

Results of a single site Phase II clinical trial in patients with moderate to severe disease showed that oral administration of Alequel™ appeared to reduce inflammation in the intestine by inducing immunological tolerance. Patients were monitored for disease activity using the standard Crohn’s Disease Activity Index (CDAI), a quality-of-life questionnaire, Inflammatory Bowel Disease Questionnaire (IBDQ).

The primary endpoint of the study was the remission rate, defined as a CDAI score of 150 or lower at 2 consecutive time points 3 weeks apart:

The study also met secondary endpoints for improved quality of life as measured by IBD scores, as well as overall safety and tolerability. No treatment-related adverse events were noted.

Optiquel ™

OptiquelT, based on Enzo’s immune regulation technology platform, is an oral formulation designed as a potential treatment for autoimmune uveitis, an intraocular inflammatory condition that reduces visual acuity and can lead to blindness. The active ingredient in Optiquel,T B27PD, is a small peptide that has been shown to mimic the retinal S-antigen, the offending protein antigen responsible for the ocular inflammation. Intraocular uveitis appears to result from an autoimmune reaction to antigens in the eye, specifically the S-antigen and the interphotoreceptor-retinoid-binding-protein (IRBP). OptiquelT has been designed to down regulate this undesired autoimmune response by inducing a specific immune tolerance to the retinal S-antigen. Reduction of intraocular inflammation by down-regulation of the autoimmune response has the key advantage of avoiding the side effects associated with treatment by systemic steroids and immunosuppressive agents.


Pre-clinical testing revealed no potential for adverse reactions, and the drug was well tolerated and no adverse effects were observed in an investigator-initiated pilot clinical trial of 9 autoimmune uveitis patients. The results of this pilot study demonstrated the potential of OptiquelT to ameliorate intraocular inflammation with the added benefit of a reduction of the required corticosteroid dosage.

OptiquelT has been granted orphan status in Europe and we will apply for the same in the U.S. since orphan status designation can confer both financial and marketing benefits.

Based on favorable preclinical animal studies and the pilot clinical trial, a CRADA between Enzo and the National Eye Institute was established to perform a proof-of-concept clinical trial. The trial is being led by Dr. Robert Nussenblatt, one of the world’s foremost authorities on uveitis.