MitoTarget: The European Commission has awarded a three year grant of nearly EUR 6 million to support a 3 year collaborative project named MitoTarget, which will be carried out by a consortium led by Trophos. MitoTarget forms part of the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities and will investigate the efficacy and safety of Trophos compound TRO19622 in a clinical study in Amyotrophic Lateral Sclerosis (ALS) patients, and develop the understanding of mitochondrial dysfunction and therapeutic potential of a novel proprietary class of molecules in neurological diseases.
MS-Repair: A further EUR 800,000 will come from France's Agence Nationale pour la Recherche (ANR) to study the potential of its proprietary cholesterol-oxime compounds in in-vivo models of multiple sclerosis (MS). The two year collaborative project called MS-Repair, will seek to establish preclinical proof of principle for Trophos proprietary compounds in models of MS.
Trophos expects both projects to provide proof of principle, and that a new class of therapeutic agents targeting mitochondrial dysfunction in neurons or their supporting cells, could have wide ranging therapeutic benefits and commercial potential.
"We are delighted with the vote of confidence shown by these two grants in Trophos and its neuroprotection programs," said Damian Marron, CEO at Trophos. "The European Commission, after extensive expert evaluation, has chosen to support the MitoTarget project, and Trophos is very pleased to be collaborating with a distinguished panel of academic and clinical investigators on furthering our understanding of the potential of this proprietary class of drug candidates, notably through the important ALS clinical trial that will take place with Trophos' lead molecule, TRO19622."
"Recently published clinical studies support the therapeutic rationale for mitochondria-targeted drugs in both neurology (Alzheimer's disease) and cardiology (ischemia-reperfusion injury), and Trophos is uniquely placed to explore the validated therapeutic and commercial potential of this emerging field to create value for patients, the medical community and our investors," added Marron.
Trophos is leading a consortium of five basic research centers and 14 clinical centers at 16 institutions around Europe specializing in research and/or healthcare. MitoTarget's main aims are to i) demonstrate the therapeutic efficacy and safety of TRO19622, a novel mitochondrial pore modulator, in Amyotrophic Lateral Sclerosis (ALS) patients and, ii) to gain a greater understanding of the role of mitochondrial dysfunction in neurodegenerative diseases and of the therapeutic potential of a proprietary class of mitochondrial pore modulator, cholesterol-oxime compounds, to treat other indications such as Alzheimer's Disease.
The ALS clinical study will be sponsored by Trophos and performed by a consortium of prominent European clinical investigators, all of whom have extensive prior experience conducting and collaborating in large multi-centre clinical trials in ALS. The trial will assess safety and efficacy with a primary end-point of improvement of survival at 18 months. Trophos has been granted orphan drug designation for TRO19622 for the treatment of ALS by the U.S. Food and Drug Administration and 'Orphan Medicinal Product' designation for both ALS and SMA by the European Commission in the EU. The trial protocol has also been the subject of an EMEA Protocol Advice procedure.
The basic research component of MitoTarget will characterize mitochondrial function in neurons to better understand how mitochondrial dysfunction, leading to oxidative stress and activation of cell death pathways, is implicated in various neurodegenerative diseases and aging. Using preclinical model systems, partners will investigate the ability of the new class of cholesterol-oxime compounds discovered by Trophos to correct mitochondrial dysfunction and promote neuron survival and axonal growth.
MS-Repair is a collaborative research project coordinated by Trophos and supported by the French ANR that will explore the potential of Trophos compounds, including TRO19622, to provide significant benefit in preclinical demyelination models of multiple sclerosis. Positive evidence of efficacy in these models will provide the necessary proof of principle to motivate further clinical development of these compounds for treatment of MS.
TRO19622 is representative of Trophos' proprietary, mitochondrial pore modulator, cholesterol-oxime compounds that were identified in the neuronal cell screening platform developed at Trophos. Preclinical studies have demonstrated that these compounds promote the function and survival of neurons and other cell types under disease relevant stress conditions (Bordet et al., JPET 322:709-720, 2007) through interactions with the mitochondrial permeability transition pore (mPTP).
TRO19622 has successfully completed phase I studies in healthy volunteers and phase Ib studies in ALS and SMA patients. These clinical trials demonstrated that the product is well tolerated, has an excellent safety profile and that once-a-day oral dosing achieves the predicted exposure level required for efficacy, based on preclinical models. Drug interaction studies with riluzole, the only registered treatment for ALS, showed no impact or interaction of TRO19622 on riluzole pharmacokinetics.
About ALS (Amyotrophic Lateral Sclerosis)
ALS, more commonly known as Lou Gehrig's disease in the USA, is a progressive and fatal neurological disease that is estimated to affect over 100,000 people worldwide. There is no cure for ALS. The only drug approved for ALS is riluzole (Sanofi-Aventis), which has been demonstrated to give a 2- 3 month survival benefit to ALS patients. For more information about ALS, see www.alsa.org
About Multiple Sclerosis
Multiple sclerosis is an autoimmune condition that affects the transmission of messages from the central nervous system to the rest of the body. MS has a prevalence between 2 - 150 per 100,000, is more common in women and usually manifests itself in young adults between 20 and 40 years of age. Sufferers experience recurrent episodes of inflammation and destruction of the myelin sheath that surrounds and protects nerves, resulting in progressive dymyelination. There is no cure for MS, approved disease-modifying treatments are modestly effective at decreasing the number of attacks and slowing disease progression, and have various adverse side effects. For more information about MS, see here.
Trophos is a clinical stage pharmaceutical company developing innovative therapeutics for indications with underserved needs in neurology and cardiology. The Company has a novel and proprietary cholesterol-oxime based chemistry platform generating a pipeline of drug candidates, with a lead product, TRO19622, in phase II clinical trials. Trophos' mitochondrial pore modulator compounds enhance the function and survival of stressed cells via modulation of dysfunctional mitochondria through interactions at the permeability transition pore (mPTP). Recently published clinical studies support the therapeutic rationale for mitochondria targeted drugs in neurology (Alzheimer's disease) and cardiology (ischemia-reperfusion injury). Trophos is uniquely placed to exploit this validated therapeutic approach with its proprietary chemistry platform targeting the mitochondria.