Introduction

Avexxin builds its novel therapeutic approach on a deeper understanding of the extra- as well as intracellular mechanisms causing inflammatory disease in general and psoriasis in particular, which has been obtained through more than a decade of research at Prof. Berit Johansen’s laboratory at the Norwegian University of Science and Technology (NTNU). With the sequential understanding of the disease causing process in psoriasis including:

               Antigen -> immune cells  ->  skin keratinocytes

Avexxin now introduces new small molecule compounds targeting a novel intervention point in the disease end-point, the hyperproliferating skin keratinocytes (see figure 1). This is one step further downstream compared to biologics, which targets immune cells and their secreted cyokines (e.g. TNF) in the circulatory system. The latter explaining many of the adverse effects observed with this therapy. The Avexxin intervention point lies within the proinflammatory intracellular signaling cascade in human skin keratinocytes, induced by TNFα. Encompassed by this novel therapeutic strategy Avexxin believes that it addresses the need for novel, highly specific, therapy in the treatment of several inflammatory conditions.

Figure 1 illustrates the target of the Avexxin treatment focus. The Avexxin therapeutic approach is believed to attenuate the keratinocyte TNFα  initiated proinflammatory intracellular signaling cascade leading to transcription factor NF-kB activation, however still rendering the parallel intracellular signaling cascades intact. The specific point of action of Avexxin’s lead compound is the proinflammatory group IVα phospholipase A2 (IVαPLA2) enzyme. Research has confirmed that PLA2 enzyme expression, activity, and product accumulation coincide with disease severity, suggesting successful use of the Avexxin compounds both in treatment of mild, moderate and severe psoriasis as well as in other chronic inflammatory disorders.

Figure 1: Action of Avexxin compound