Purpose: To investigate TRS as a potential drug candidate with novel mechanism of action, for treatment of uveitis in patients with uveitis glaucoma. Ocular inflammation presents a severe, sight-threatening medical challenge. There is an urgent need for an effective and safe anti-inflammatory drug, specifically for 20-40% of uveitis patients that develop glaucoma. TRS (Tuftsin-Phosphorylcholine) is a novel drug, inspired by nature. It is a conjugate of two potent anti-inflammatory molecules with a synergistic affect.

Methods: Efficacy of TRS was evaluated using a series of in-vivo autoimmune animal models including experimental autoimmune uveitis (EAU), compared to PBS and/or active control. these were also combined with ex-vivo studies on human samples, as well as in-vitro studies in macrophage cell-lines / PBMCs. Safety and tolerability of TRS01 (TRS eye drops) was evaluated through in-vivo GLP toxicology studies in NZW rabbits and beagle dogs, as well as in-vitro GLP genotoxicity and phototoxicity studies with TRS (API).

Results: TRS was found to induce macrophage shift from inflammatory state to IL-10-secreting anti-inflammatory state (M1→M2 shift) and promote the resolution of inflammation in animal models including EAU.

In-vivo GLP toxicology studies demonstrated the safety and tolerability of TRS01 (TRS eye drops, the clinical route of administration) in the two most relevant species. TRS was found to be non-mutagenic and non- phototxic in the in-vitro test systems .

Conclusions: The pre-clinical safety and efficacy studies support the clinical evaluation of TRS01 formulations. TRS01 is currently being evaluated in two phase I/IIa multicenter, randomized, double-masked clinical studies for the treatment of non-infectious anterior uveitis and post-surgical ocular inflammation.