Immunotherapy in IMIDs

A major unmet medical need

Immune-mediated inflammatory diseases (IMIDs) – affecting millions of people

Immune-Mediated Inflammatory Diseases (IMIDs) represent a major unmet medical need: An estimated 50 million people are affected in the Western industrialized countries, worldwide there are more than 300 million patients.

IMIDs present as a variety of diseases, for example psoriasis, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. Most IMIDs can become chronic. Symptoms include: Pain, discomfort, organ damage, loss of quality of life, increased co-morbidity, and shortened life expectancy.

For a long time, IMIDs were considered unrelated diseases. Only in the last ten years, advances in inflammation research and new insights into the immune system have shown that there is a common disease pathway. This common pathway, however, may affect and harm very different organ functions.
The commonality lies in a dysregulation of signaling pathways in the immune system. Therefore, this group of originally unrelated inflammatory diseases is now regarded as a common challenge.

The discovery of a common pathway has opened the door for the development of superior therapies - in the future it will be possible to effectively treat entirely different IMIDs with a single drug.

A safer approach to immunotherapy

The human immune system consists of two distinct subsystems: the innate immune system and the adaptive immune system.
The innate immune system is the evolutionary older part of the immune defense. It primarily recognizes common patterns of disease causes and can react immediately. Patterns to which the innate immune system reacts can be injuries, physical stress, bacteria, or autoimmune triggers.

Central to the chronic progression of IMIDs is a dysregulation of the immune response to injury, infection, or autoimmune triggers.
Despite the fundamental role of the innate immune defense, the adaptive immune system, with B-cells and T-cells as its central players, has been the focus of most immune research and immune-related therapies during the past 30 years. While therapies directed at T-cell and B-cell function offer the potential of high efficacy, they also carry an increased risk of severe side effects.

Only in recent years the decisive role of the innate immune system in driving and maintaining IMIDs has been fully recognized. Therapies that modulate the activity of the innate immune response have the potential to be simultaneously effective for many if not all IMIDs while being very safe and well tolerated – an important aspect for medications that often have to be taken for years.
MetrioPharm is one of the first immune-therapy companies that focuses on developing new drugs specifically designed to modulate the innate immune system.

MetrioPharm's MP1000 platform targets macrophages – a new disease-modifying paradigm

The primary target of drug molecules from MetrioPharm's MP1000 platform is the macrophage. Macrophages are the central cell type of the innate immune system. When they are activated, macrophages change into their inflammatory M1 state. If they remain in this state for too long, they will drive an inflammation that can cause organ damage.

A hallmark of immune-mediated inflammatory diseases is a vicious cycle in which macrophages stay constantly activated in their M1 state. The inflammation, disease symptoms, and tissue damage become chronic.

Molecules of MetrioPharm's MP1000 drug platform, including our lead compound MP1032, have the ability to modulate the H2O2-mediated activation state of macrophages and downregulate the M1 state. In contrast to other immune-modulating and disease-modifying drugs, MP1032 is an oral immune-sparing drug candidate. It affects macrophages at the site of inflammation only and does not increase susceptibility to infections.

MP1032 was well tolerated in a phase I clinical trial. Further clinical trials are ongoing.