Transition commences dosing in TT-301 Phase 1 clinical study for rheumatoid arthritis, ICH, TBI

Transition Therapeutics Inc. ("Transition" or the "Company") (Nasdaq:TTHI) (TSX:TTH) announced today that the first patient has been dosed with drug candidate TT-301 in a Phase 1 clinical study. TT-301 is a small molecule compound that has demonstrated efficacy in preclinical models of rheumatoid arthritis, intracerebral haemorrhage ("ICH") and traumatic brain injury ("TBI"). In pre-clinical studies, TT-301 has been shown to act by inhibiting the overproduction of inflammatory cytokines, such as interleukin-1 (IL-1Beta), tumour necrosis factor-alpha (TNF-Alpha), a key disease process associated with many inflammatory and degenerative diseases. 

The Phase I trial is a double blind, randomized, placebo controlled study in which healthy volunteers will receive placebo or escalating doses of intravenously administered TT-301. The primary objectives of the trial are to evaluate the safety, tolerability and pharmacokinetics of TT-301.

The data from Phase I studies are a first step in the development of TT-301 for central nervous system (CNS) intravenous indications, ICH and TBI. In well-established rodent models of chronic neuroinflammatory disorders, treatment with TT-301 reduced recruitment of activated microglia, reduced cerebral edema and improved motor skills and neurocognitive outcomes. The goal of intravenously administered TT-301 is to provide a short-term treatment, that following CNS injury, can reduce destructive glial cell derived inflammatory cycles, and their long-term neurotoxic effects.  

In follow up studies, the Company plans to advance oral formulations of lead drug candidates TT-301 or TT-302 for inflammatory diseases such as rheumatoid arthritis. Both TT-301 and TT-302 are novel, orally available, small molecule compounds that can suppress inflammatory cytokine production, reduce inflammation and improve outcomes in preclinical models of collagen-induced arthritis.   Currently, Phase 1 enabling preclinical studies are being performed for oral forms of both compounds.