CLINICAL PROGRAMS – CHRONIC INFLAMMATION
The role of C5a for chronic inflammation has been more clearly identified in the recent years such that C5a has become a very attractive target for chronic – and auto-immune inflammatory diseases. This is largely because of its described effects on T-cell function, causing a substantial dysbalance and shift towards pro-inflammatory T-cell responses. In addition, many chronic inflammatory diseases are burdened by flare phases with intensified inflammation causing tissue damage which is often promoted by auto-activation of neutrophils.
Blocking C5a therefore delivers various potentially benefitial effects in chronic inflammtory diseases as it has been shown to re-establish T-cell balance by increasing regulatory T-cells and decreasing pro-inflammatory Th-17 and Th-1 responses and because of its strong potential to control neutrophil activation besides many other important described anti-inflammatory mechnisms.
IFX-1, the company´s first-in-class anti-human C5a monoclonal antibody is currently being developed in 2 disclosed and other undisclosed chronic inflammatory diseases whithin the orphan drug and auto-immmune disease space. InflaRx thereby focuses on diseases with high unmet medical need.
CLINICAL PROGRAMS - ACUTE INFLAMMATION
IFX-1 is currently under development in two different acute inflammatory indications based on the well described role of C5a for the acute inflammatory response and has completed one clinical phase IIa study in a third acute care indication.
ABOUT COMPLEX CARDIAC SURGERY
SIRS Prevention in Complex Cardiac Surgery is an unprecedented indication within the Acute Care field under development at InflaRx. It is defined by a list of complex open heart combination surgical procedures requiring the use of a heart-lung machine (cardiopulmonary bypass “CPB”) with long cardiac bypass times. Hereby, the blood is bypassing the heart and lung in heparin coated tubes while being oxygenated outside the human body with specific membranes.
During complex cardiac surgery, complement is strongly activated via two mechanisms: 1) contact with the artificial surfaces of the tubes and membranes of the heart-lung machine, and 2) the extensive tissue injury during such invasive surgery. This leads to a substantial terminal complement activation and generation of C5a, resulting in a strongly aggravated systemic inflammatory response syndrome (SIRS). The phenomenon of a substantial inflammatory response is generally recognized in large scale surgery in various different surgical disciplines but it is especially pronounced in complex cardiac surgery. Currently, there is no approved drug addressing this unmet medical need.
Patients undergoing complex cardiac surgery frequently suffer from this inflammatory response, which can causes a life-threatening situation, affecting the cardiovascular and other organ systems, leading to prolonged ventilation times and other detrimental secondary organ dysfunctions. C5a is believed to be the key “boosting” factor for this inflammatory response. Thus, preventive pre-operative treatment with IFX-1 holds the potential to intercept C5a and to prevent C5a from exerting this well described aggravation function.
IFX-1, a first-in-class anti human C5a monoclonal antibody developed by InflaRx, is currently being studied in a multi-center double blinded placebo controlled clinical phase II trial in 100 patients undergoing Complex Cardiac Surgery to evaluate different doses of preventive treatment with IFX-1 and its effect on surrogate and clinical endpoints.
LESSONS FROM SEPTIC ORGAN DYSFUNCTION
In a first biological proof of concept PK/PD trial in patients suffering from pulmonary or abdominal infections and early septic organ dysfunction, IFX-1 highly significantly inhibited C5a and demonstrated to be safe and well tolerated. This multi center dose escalation double blind placebo controlled study recruited 72 patients (16 patients per dosing group plus 8 placebo patients for each dosing group) and was a first-of-its-kind study in this infectious disease field because patients were recruited and put on study drug within 3.5 h after screening. Besides reaching all primary endpoints, IFX-1 administration resulted in benefit trends in laboratory parameters (cytokines) as well as in clinical endpoints for which the study was not powered to demonstrate statistical significance. The results from this ground breaking study gave insight into complement consumption and IFX-1 PK profiles in acutely ill patients suffering from abdominal and pulmonary infections and laid the ground for the clinical development program in sCAP.