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Trophos Publishes ALS Article in Journal of Pharmacology and,Experimental Therapeutics

Trophos Describes Identification, Characterization and Broad Neuroprotective Properties of TRO19622 in Journal of Pharmacology and Experimental Therapeutics

Neurodegenerative Disease Specialists Publish Details of a Novel Drug Candidate for ALS That Targets Mitochondrial Proteins

MARSEILLE, June 19th, 2007 - Trophos SA, a biopharmaceutical company specializing in the discovery and development of drugs for neurological disorders, announced today that a publication entitled "Identification and characterization of TRO19622 (cholest-4-en-3-one, oxime), a novel drug candidate for amyotrophic lateral sclerosis" has been accepted and published online May 11, 2007 in the Journal of Pharmacology And Experimental Therapeutics (J Pharmacol. Exp. Ther. 2007 May 11; [Epub ahead of print]).

Amylotrophic 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 about 100,000 people worldwide. There is no cure for ALS. The only drug approved for ALS is riluzole (Rilutek(R), Sanofi-Aventis), which has been demonstrated to confer some survival benefit to ALS patients.

The studies reported in the paper by Bordet et al., (see below) identify two protein targets of TRO19622 present in the outer mitochondrial membrane suggesting that the compound has potential in a range of additional commercially attractive therapeutic indications involving mitochondrial dysfunction, including painful neuropathies. The publication describes the models of motor neuron disease employed to support the use of this compound to treat ALS, as well as spinal muscular atrophy. TRO19622 is currently in a Phase IIa clinical trial to establish its efficacy as a treatment for painful diabetic neuropathy.

TRO19622 is representative of novel compounds identified using the proprietary neuronal cell screening platform developed at Tr ophos. In vitro, TRO19622 promotes motor neuron survival in the absence of trophic support in a dose-dependent manner. In preclinical models in vivo, TRO19622 rescues motor neurons from axotomy-induced cell death in neonates and promotes nerve regeneration following sciatic nerve crush. Furthermore, in the SOD1G93A model of familial ALS, TRO19622 treatment improves motor performance, delays the onset of the clinical disease, and extends survival.

TRO19622 binds directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel (VDAC) and the translocator protein (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity.

TRO19622 has successfully completed Phase I/Ib studies in both healthy volunteers and ALS patients demonstrating the product is well tolerated, has an excellent safety profile and that once-a-day dosing achieves the predicted exposure level required for efficacy, based on preclinical models. These data support the further clinical evaluation of TRO19622 as a potential treatment for ALS.

"Trophos is proud to have this body of work accepted for publication in a well recognized journal such as JPET," said Rebecca Pruss, CSO at Trophos. "Given the significant unmet medical need in ALS, it is tremendously encouraging that TRO19622 promotes the survival of motor neurons in this extensive battery of preclinical models. These studies, along with the excellent clinical safety profile of TRO19622, provide the basis upon which Trophos plans to initiate a pivotal Phase II/III trial to establish the clinical efficacy of TRO19622 in ALS patients."

Pruss added: "Moreover, we are particularly excited that there is increasing preclinical evidence that the mitochondria-mediated mechanism of action of TRO19622, and other compounds in this class, will have huge commercial potential in other chronic neurological disorders, such as neuropathic pain, and non-neurological conditions, such as ischemia-reperfusion injury and hepatitis."

Author List: Thierry Bordet, Bruno Buisson, Magali Michaud, Cyrille Drouot, Pascale Galea, Pierre Delaage, Esther-Marie Steidl, Delphine Maux, Michel Delaage, Rebecca M. Pruss (Trophos), Natalia P. Akentieva, Alex S. Evers, Douglas F. Covey (Washington University School of Medicine), Mariano A. Ostuni, Jean-Jacques Lacapere (U773 Inserm), Charbel Massaad, Michael Schumacher (UMR788 Inserm), Christopher E. Henderson (Center for Motor Neuron Biology, Columbia University)

About Trophos: <http://www.trophos.com>www.trophos.com Trophos is a biopharmaceutical company committed to the discovery and development of novel therapeutic compounds to treat neurological disorders and other diseases with high unmet medical needs. Trophos has pioneered an innovative phenotypic screening platform which has enabled it to develop a proprietary portfolio of products, such as our lead product TRO19622, that confer a survival benefit upon both neuronal and non-neuronal cell types (such as cardiomyocytes & hepatocytes) through a mitochondria-based mechanism of action with a robust therapeutic rationale, one that is predicted to exhibit a therapeutic benefit in diseases such as neuropathic pain, ischemia-reperfusion injury and hepatotoxicity. The company is focusing its efforts on the orphan indications, ALS, SMA & Huntington's disease, while seeking to establish clinical proof of concept in indications such as neuropathic pain, ischemia-reperfusion injury and hepatotoxicity.

Trophos was founded in 1999, is based in Marseille, France and currently has 32 employees. -- -- Best regards,

Katie Ollerenshaw ANDREW LLOYD & ASSOCIATES http://www.ala.com katie@ala.com

Brighton Business Centre 95 Ditchling Road Brighton BN1 4ST ENGLAND Tel: +44 1273 675100 Fax: +44 1273 675400

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