Topline results for olesoxime as add–on therapy to Interferon beta are expected in early 2014

Trophos SA, a clinical stage pharmaceutical company developing innovative therapeutics from discovery to clinical validation for indications with under-served needs in neurology and cardiology, announces today that they have completed enrollment in the Translate MS-Repair Phase Ib multiple sclerosis (MS) trial.
 
The trial is a randomized, placebo controlled, Phase Ib study in multiple sclerosis (MS) patients treated with Trophos’ olesoxime as an add-on therapy to Interferon beta. In three months, 44 patients have been recruited in three investigational sites in France. The first subject was enrolled on April 2 and the last subject on July 11, 2013.
 
Though many disease-modifying treatments effectively address the inflammatory episodes in relapsing remitting MS, they have almost no effect on the long term disability associated with MS resulting from progressive neurodegeneration. Promoting remyelination and providing neuroprotection are new concepts for the treatment of MS. Trophos’ olesoxime is the most advanced oral small molecule to demonstrate these activities in relevant preclinical models.
 
The Phase Ib study will evaluate safety, tolerability and PK data of a six month treatment with olesoxime in MS patients stably treated with interferon beta. In addition, the study is also planned to analyze multi-center feasibility of potential imaging biomarkers as surrogate outcome measures.
 
The 24 month Translate MS-Repair project is funded by the French Agence Nationale de Recherche (ANR) through their Recherches Partenariales et Innovation Biomedicale 2012 program. The Translate MS-Repair consortium is led by Trophos and includes Assistance Publique Hopitaux de Marseille, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Universitaire de Reims, Centre National de la Recherche Scientifique, Institut national de recherche en informatique et en automatique.
 
"Completing recruitment in this clinical study so rapidly is a great achievement and a major step in the development of olesoxime as a potential treatment for neurodegeneration and myelin repair in MS," said professor Jean Pelletier, Assistance Publique Hopitaux de Marseille, the principal investigator for this study. "All the partners involved, Trophos, clinical research teams and MRI centers are highly motivated and have worked hard to initiate this study. We can now anticipate that the top line results will be available in the first half of 2014 and that will pave the way for the further clinical development of olesoxime in MS patients.”
 
This randomized, double-blind, placebo-controlled, six month study will assess safety, tolerability and pharmacokinetics of six months treatment with 495 mg/day olesoxime in relapsing remitting MS patients who are stably treated with any form of Interferon beta (Avonex(R), Rebif(R), Extavia(R), Betaseron(R)).  
 
An additional objective of the Translate MS-Repair project is to survey a number of non-conventional MRI techniques for the use in future multicenter trials as biomarkers of neuroprotection and/or myelin repair. Use of such techniques as Magnetization Transfer Ratio (MTR), Diffusion Tensor Imaging (DTI) or 23Na-MRI in combination with conventional MRI techniques such as gadolinium-enhanced T1- and T2-weighted MRI may provide new tools to assess neuroprotective and/or restorative treatments in MS or other neurodegenerative diseases. Exploratory analysis of preliminary efficacy data with olesoxime will provide some results to be used for planning the Phase II and III program.
 
"This trial is funded by a second EUR 1 million grant we received from the ANR to support the development of olesoxime for the treatment of MS. The Translate MS-Repair project follows the results generated by the first Trophos’ led consortium project, MS-Repair. These results showed convincing evidence that olesoxime promotes myelin repair in multiple preclinical demyelinating disease models,” said Rebecca Pruss, chief scientific officer, Trophos. “The Phase Ib study is a prerequisite to a future Phase II study to evaluate if olesoxime could activate remyelination and consequently prevent long term disability in MS patients.”

“Trophos has a long history of building consortia from a network of scientists and clinical investigators to target a range of therapeutic targets. The Translate MS-Repair and MS Repair projects are the most recent examples of this consortia-based approach,” said Christine Placet, CEO, Trophos. “Trophos’ olesoxime has demonstrated great promise as a potential treatment for a variety of neurodegenerative diseases. In addition to this study in MS patients, olesoxime is being studied in SMA patients. Combined with the compound TRO40303 that is targeting cardiac ischemia-reperfusion injury, this generates a considerable market potential of nearly USD 2 billion for the conditions targeted by our pipeline.”

About the Translate MS-Repair study
The Phase Ib study is a randomized, placebo-controlled, double blind study planned to evaluate tolerance, safety and PK data of olesoxime in relapsing remitting MS patients stably treated with any form of interferon beta. The study will evaluate conventional endpoints such as relapse rate and lesion load measured by MRI. The study will also assess the feasibility of performing non-conventional MRI including MTR, DTI and 23Na-MRI. The Translate MS-Repair project is a partnership between Trophos, three clinical research teams led by professor Jean Pelletier in Marseille (APHM, CHU La Timone), professor Gilles Edan, CHU Rennes and Dr. Ayman Tourbah, CHU Reims and two MRI teams in Marseille (professor Jean-Philippe Ranjeva, APHM/CNRS and CEMEREM-CRMBM) and Rennes (professor Christian Barillot, INRIA VISAGES). It will pave the way for future Phase II and Phase III clinical trials to assess the ability of olesoxime to promote repair and prevent neurodegeneration underlying progressive disability in MS patients.

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About Olesoxime
Olesoxime (TRO19622) is a mitochondrial targeted, cholesterol-like compound that is currently undergoing clinical evaluation for the treatment of spinal muscular atrophy. Olesoxime’s safety and tolerability has already been tested in 15 clinical trials involving 968 patients or healthy volunteers and proved to have an excellent safety profile. The mechanism of action of olesoxime involves prevention of mitochondrial dysfunction and improved microtubule dynamics, both implicated in neuroprotection and oligodendrocyte maturations. Studies in preclinical models showing that olesoxime favors myelination were reported by Trophos and colleagues in Annals of Neurology

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About Multiple Sclerosis
MS is a chronic inflammatory disease of the central nervous system leading to demyelination and axonal degeneration. When myelin is destroyed, it leaves random areas of scar tissue (sclerosis) that affect the ability of nerve cells to communicate with each other. This results in the blocking of neurological transmissions leading to physical and cognitive disability. It is estimated that approximately two million people worldwide suffer from MS. Most of them are 20 – 40 years old with females outnumbering males by 2:1 ratio. The majority of MS patients are initially diagnosed on the basis of recurring inflammatory episodes (relapsing remitting MS), but about 50 per cent will show progressive disability even in the absence of inflammatory relapses (secondary progressive MS); others present with progressive neurological symptoms typical of MS without an episodic inflammatory history (primary progressive MS). Although there are now many approved therapies for the treatment of RRMS, they have not proved to significantly and curatively change the rate of disability progression, leading to severe handicap in MS patients.

About Trophos:
Trophos is a clinical stage pharmaceutical company developing innovative therapeutics for indications with under-served needs in neurology and cardiology. The company has a novel and proprietary cholesterol oxime based chemistry platform generating a pipeline of drug candidates, with the lead product, olesoxime (TRO19622), receiving orphan drug status from EMA and FDA for Phase II/III development for spinal muscular atrophy, a rare neurological disease, and TRO40303, in Phase II clinical development, to treat cardiac reperfusion injury following angioplasty to treat acute myocardial infarction; this study is part of an EC FP7 funded translational research project called MitoCare (HEALTH-F2-2010-261034). Trophos' proprietary, cholesterol-oxime family of compounds enhances the function and survival of stressed cells and favors neuronal and oligodendrocyte maturation. Trophos was founded in 1999 and is based in Marseille, France.

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