Trophos announces today an EU award of €6 million to support its MitoCare project, which is investigating a drug to treat cardiac ischemia reperfusion injury (IRI) as well as developing biomarkers and models of IRI. Work under MitoCare will begin in January 2011.
Trophos is leading the MitoCare consortium, which comprises nine clinical centers, three basic research centers, and four SME’s (including Trophos). It will evaluate the therapeutic efficacy and safety of TRO40303, a cholesterol oxime mitochondrial pore modulator, in a Phase II POC study in acute myocardial infarction (MI) patients.
The TRO40303 clinical program is sponsored by Trophos. Results from the Phase I study are expected in the first quarter of next year.
The Phase II placebo-controlled trial will be conducted in acute MI patients with large myocardial infarct undergoing percutaneous transluminal coronary angioplasty during percutaneous coronary intervention, where TRO40303 will be administered as a single IV infusion prior to the reperfusion by angioplasty.
MitoCare scientists will also conduct research on biomarkers and predictive and confounding factors of response in humans, analyze new markers for necrosis and heart failure, analyze variability in preclinical models, and compare human and preclinical data to identify the most predictable preclinical models.
Trophos’ pipeline of mitochondrial pore modulators is composed of a series of cholesterol-oxime compounds that were identified in the neuronal cell screening platform developed at Trophos to enhance the function and survival of stressed cells via modulation of dysfunctional mitochondria through interactions at the permeability transition pore (mPTP).
Trophos reported in the Journal of Pharmacology and Experimental Therapeutics that TRO40303 binds directly to the cholesterol site of the mitochondrial outer membrane protein, TSPO, which is associated with the mitochondrial permeability transition pore and is highly expressed in the heart, allowing rapid uptake of TRO40303 into cardiac tissue.
In vitro TRO40303 improved oxidative stress-induced cardiomyocyte survival that was correlated with a reduction in reactive oxygen species production, slowed triggering of mitochondrial permeability transition, as well as reduced cytoplasmic and mitochondrial calcium overload and apoptotic factors. A preclinical model of MI treatment with TRO40303 at the time of reperfusion was shown to significantly reduce infarct size.
Trophos’ lead product, TRO19622, is also based on its cholesterol oxime chemistry platform. It is in Phase III development for ALS as part of an EU-funded project, MitoTarget. It is also being studied in spinal muscular atrophy and is currently in a Phase I trial funded by the Association Francaise contre les Myopathies.