New safe and effective topical combo therapy for psoriasis - High efficacy without steroids

The main purpose of the project has been to develop and validate a new, safe and effective local treatment that combines AVX001 and calcipotriol, as a new therapeutic approach for the treatment of mild to moderate psoriasis. Proof-of concept for the effect of AVX001 monotherapy in psoriasis was found in 2015 (phase I / IIa studies). Psoriasis is a common, chronic and debilitating skin disease that affects ~ 2% of the global population (125 million people). Topical therapy (eg, Vitamin D3 analogues (e.g., calcipotriol) and corticosteroids) is associated with safety concerns, tolerance / irritation problems and dose limitations. The innovation is based on a unique and novel therapeutic point of attack in the pro-inflammatory signaling cascade: intracellular enzyme group IVA cytosolic phospholipase A2 (cPLA2a). Unpublished observations in our laboratory have shown that AVX001 / calcipotriol combination therapy has a significant synergistic effect superior to calcipotriol and betamethasone. Furthermore, since the current treatment contains steroids, the current treatment cannot be used continuously. Coegin Pharma's new treatment, however, will. Coegin Pharma's use of group IVA cPLA2 inhibitors represents an important therapeutic innovation for patients by reducing symptoms and discomfort, and reducing some of the psychosocial burdens these diseases cause. Research / development tasks have included a) validation of combination therapy of AVX001 / calcipotriol - in vitro, in vivo, and ex vivo, b) mechanistic and biomarker studies, c) large-scale GMP synthesis, d) preclinical toxicology and safety studies , and e) planning a clinical plaque study for dose optimization. Progression of validation of combination therapy, as well as mechanistic and biomarker studies and tox studies have proceeded as planned, showing very interesting data. Two separate mechanisms have been identified where cPLA2 inhibitor stops the growth of skin cells while calcipotriol stops layer division. Identification of these mechanisms is important to understand the synergistic effect of the two inhibitors in combination, they act on complementary biological processes, which can be exploited in several hyperproliferative skin diseases. Furthermore, an environmentally friendly GMP flow synthesis has been developed. Against this background, Coegin Pharma is looking at expanding its scope for innovation beyond psoriasis. Topical treatment of skin cancer precursors is one such indication.

Coegin Pharma har med dette prosjektet bidratt vesentlig med å forstå mekanismene for virkemåten av AVX001 og calcipotriol, både alene og i kombinasjon. Coegin Pharma har utvidet sin produktportefølje og ser muligheter for ny produktutvikling innen andre hudsykdommer inkl. hudkreft. Coegin Pharma har også utvidet og styrket sitt internasjonale nettverk, samt styrket samarbeidet med norsk industribedrift. De langsiktige virkninger og følgeeffekter av prosjektet er klinisk uttesting av en potensielt ny medisin bestående av AVX001 og calcipotriol for behandling av mild-til moderat psoriasis. En slik behandling vil betydelig redusere ugunstige bieffekter ved langvarig corticosteriodbehandling. Coegin ønsker videre å forfølge hudkreft som indikasjon for å videreutvikle vår produktportefølge og fremtidig bruksområde.

The principal objective of the project is to develop and validate a novel safe and effective topical treatment combining AVX001 and calcipotriol, as a new therapeutic approach to treat mild-to-moderate psoriasis. In 2015, Avexxin achieved Proof-of-Concept in man in psoriasis for AVX001 as monotherapy (phase I/IIa trials). The independent safety board found the mono treatment to be remarkably safe. Psoriasis is a common, chronic and disabling skin disorder affecting ~2% of the global population (125 million people). Current topical therapy (e.g. Vitamin D3 analogs and corticosteroids) is associated with safety issues, tolerability/irritation concerns and dose restrictions. The innovation is based upon a unique and novel therapeutic intervention point in the pro-inflammatory signaling cascade: the intracellular enzyme group IVA cytosolic phospholipase A2 (cPLA2a). Studies at the Avexxin lab show that the AVX001/calcipotriol co-treatment has a significant synergistic effect. Avexxin's use of group IVA cPLA2 inhibitors represents an important therapeutic innovation for the patients by reducing the symptoms and discomfort, and reducing some of the psychosocial burden these diseases entail. Project partners are Avexxin AS, Synthetica AS, NTNU and Harvard Medical School. Professor Joseph Bonventre from Harvard, who is an international pioneer in cPLA2a research, will participate in the project. Avexxin has also teamed up with leading international sub-contractors to carry out the project.