Nautilus/Creabilis collaborate on therapeutic protein
variant of CT500, a non-antibody protein with antagonist activity
against HMGB1 has been established, paving the way for
applications, to treat tumours and autoimmune diseases.
Nautilus Biotech and Creabilis Therapeutics have agreed to further develop and improve the new anti-HMGB1 variant protein, which is expected to prove effective against various acute and chronic clinical indications such as autoimmune diseases, infective diseases, sepsis, tumours, cardiovascular and also neurologic and amyloid pathologies. The terms of the agreement were not disclosed
HMGB1 is a DNA binding chemo-cytokine that has become in the last year a relevant drug target, due to its key and in some cases causative role in several pathological conditions such as arthritis. The protein is in specific competition against HMGB1 versus its receptor RAGE (Receptor Advanced Glycosylation End products)
Silvano Fumero, CEO of Creabilis Therapeutics told DrugResearcher.com: "The need for an improved performance of the protein is related to the possibility of having a protein that is more resistant to protease with better PK/PD and in lower dosage. At the moment in the market there is no specific treatment towards HMGB1."
"HMGB1 is became a relevant target due its implication in many pathologies. It is a sort of cytokine and chemokine, present in the blood in very serious state of diseases as RA and melanoma."
Nautilus' technology for protein evolution, which is based on systematic mutagenesis will be used to improve the pharmacodynamic profile of CT500. The technology has already been applied to marketed proteins, such as IFN alpha and IFN beta, improving them by single point amino-acid substitution. This has created new products with highly competitive PK/PD characteristics compared to the marketed counterparts.
Fumero added that its proprietary technology platform had already discovered a series of bent DNA/PNA chimeras and hybrids, which were now in lead optimisation phase.
"While we are now at early stage, we are looking to select the best variant in terms of enzymatic stability and biological effect. After that we are looking to test it in vivo, preclinical safety and then IND."
The improved variant of CT500 is expected to enter into pre-clinical phase, together with the DNA/PNA lead in the second half of next year.
Fumero also commented that once sufficient data on its biological and pharmacological activity had been accumulated, they would be looking for partners for further clinical development.
