Topas Therapeutics GmbH is a Germany-based and investor-funded biotech company located in Hamburg. Topas is utilizing its cutting-edge technology platform to develop a pipeline of novel therapies to treat autoimmune diseases, allergies and anti-drug immune responses. Topas proprietary drug candidates are nano-sized particles, denoted as Topas Particle-Conjugates (TPC), to which synthetic (auto)antigen-derived peptide molecules (single peptides) are conjugated. Different TPCs can be mixed, each carrying a different peptide.
The Topas approach promotes a peptide-specific tolerance induction in CD4+ as well as CD8+ T lymphocytes. This therapeutic regimen is especially suited for combating autoimmune diseases, where antigen-specific therapies are needed without compromising the patient’s general immune status. The Topas treatment approach harnesses the natural tolerance-inducing capabilities of the liver. Various cells residing in the liver, notably liver sinusoidal endothelial cells (LSECs), can naturally suppress proinflammatory activities of CD4+ and CD8+ T cells against blood-borne antigens, e.g., food-derived antigens entering the circulation. LSECs, by default, take up innocuous antigens from the circulation within a size range of 10–100 nm, they process and present the antigen-derived peptides via HLA class I and II molecules to CD8+ and CD4+ T cells, resulting in tolerization of their immunological effector responses.
Intravenous injection of TPCs serves as a particle-mediated delivery method for peptides to directly target tolerogenic LSECs. T cell epitopes coupled to TPC mimic innocuous food antigens and were shown to be preferentially taken up by LSECs and presented to circulating T cells in a tolerogenic manner. In this way, peptide-specific immune tolerance can be induced for defined immune-disease-causing antigens, aiming at the amelioration of the respective disease. The preclinical proof of concept (PoC) of this tolerance effect was demonstrated in several in vivo animal models representing either CD4+ or CD8+ T cell mediated autoimmune diseases, such as experimental autoimmune encephalomyelitis. Based on this preclinical PoC results, Topas is currently running a first clinical phase 1 study in patients suffering from Pemphigus vulgaris.
In the scope of PHOENIX, Topas will develop a new generation of TPC for optimization of application modalities and dosing.