InflaRx develops highly specific monoclonal antibodies targeting activation products of the complement system. InflaRx has made breakthrough discoveries in the area of anti-C5a antibody generation, resulting in a new class of antibodies with both exceptional blocking activities and high selectivity. This anti-C5a technology forms the backbone for a pipeline of new antibodies to address a broad variety of indications in inflammatory diseases as well as oncology.
Anti C5a Technology
The InflaRx team has discovered and globally patented a new conformational epitope within the C5a molecule allowing for generation of highly selective and potent blocking monoclonal antibodies directed against this target. These antibodies fulfill the major three requirements determined by InflaRx for generation of suitable drug candidates:
1) delivering a complete immunological blockade / inhibition of C5a induced effects - this is important because of the abundant presence and generation capacity of C5a in the human body. Antibodies not achieving this requirement will likely leave a "signaling gap" for C5a, which in any disease setting will cause strong pro-inflammatory effects, thus limiting the ability to silence this signaling axis and to achieve the desired therapeutic result.
2) being fully selective = leaving formation of the membrane attack complex intact - this is important because C5 blocking molecules that block the ability for MAC formation in the blood bear the risk of susceptibility to life threatening infections caused by encapsulated bacteria, such as meningococci and others, for patients being treated with them. The ability to leave MAC formation intact in a highly targeted blocking approach directed against C5a translates into an improved safety profile for the patient. Thus, specificity is an important consideration.
3) binding with high affinity to C5a) – this is important because C5a, once generated, is believed to interact rapidly with its receptors which are abundantly present on most cell types in the human body, which can even be up-regulated in various disease settings. Thus, a suitable anti-C5a antibody must be capable of limiting such interaction rapidly, capturing C5a before it can interact with its receptors and cause downstream pro-inflammatory signaling effects.
InflaRx's lead drug candidate, vilobelimab, is a first-in-class monoclonal antibody targeting the complement activation product C5a and is currently in clinical development for several indications.
In preclinical studies, proof of concept was demonstrated for the anti-inflammatory and tissue saving potential of vilobelimab. Vilobelimab has been proven safe and well tolerated in a double-blind placebo-controlled dose escalation Phase I study in healthy human volunteers. In a first clinical Phase IIa multi-center placebo-controlled dose escalation study in patients suffering from early septic organ dysfunction, biological proof of concept was established, demonstrating its unique C5a blocking ability as well as selectivity (leaving MAC formation intact).
Vilobelimab holds large potential for treating various inflammatory disease and certain cancers and is in clinical testing for several indications, including Hidradenitis Suppurativa, ANCA-associated vasculitis and Pyoderma Gangraenosum.
IFX002 is an advancement of vilobelimab technology, in preclinical development. IFX002 is a highly potent anti-complement C5a antibody with a higher humanization grade and altered pharmacokinetic properties.
IFX002 was developed to target chronic inflammatory diseases with high unmet medical need. Recent scientific publications suggest a fundamental role of the complement factor C5a for various neutrophil driven diseases but also for the disturbance of the T-cell homeostasis, thereby contributing to mechanisms involved in chronic and autoimmune inflammatory diseases. Therapies blocking the C5a / C5aR axis are believed to induce regulatory T-cell generation and decrease Th17- and Th1- type responses. Thus, a therapeutic anti-C5a approach would be applicable within a large variety of T-cell driven inflammatory diseases.