EXONHIT Expands Neurological Research Activities To Epilepsy

Main Category: Epilepsy
Article Date: 01 Apr 2009 - 1:00 PDT

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ExonHit Therapeutics (Alternext: ALEHT) is expanding its therapeutic research activities in neurological disorders to include epilepsy.

"An active screening program is underway with the aim of advancing a lead candidate to preclinical development by 2011," stated Dr. Loïc Maurel, President of the Management Board of ExonHit Therapeutics. "Epilepsy represents an interesting market opportunity: it affects 50 million people worldwide, and epileptic seizures remain insufficiently controlled in a lot of patients."

ExonHit has several ongoing drug development projects geared towards the treatment of neurological disorders. The most advanced compound, EHT 0202, its lead candidate in Alzheimer's disease, is undergoing Phase IIa trials. Based on promising data obtained in several animal epilepsy models, ExonHit initiated in 2008 a new research program, EHT 207, to screen new compounds with a mechanism of action similar to EHT 0202. EHT 0202 showed efficacy in several in vivo epilepsy models, and the objective of the EHT 207 program is to build off of these initial results and derive a series of new chemical entities with markedly improved efficacy.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. Dysfuntion of the GABA-ergic system plays a fundamental role in the propagation of acute seizures and in the manifestation of epilepsy syndromes. GABA agonists suppress seizures and GABA antagonists produce them.

Compounds in the EHT 207 program belong to the same chemical family as EHT 0202; they are modulators of the GABAA receptor, and are known to have anticonvulsant properties (1, 2). ExonHit demonstrated that orally administered EHT 0202 enhanced post synaptic GABA-mediated inhibition and showed anticonvulsant activity, significantly raising the seizure threshold in three different rat and mouse models. In the pentylenetetrazol (PTZ) test performed in rats, EHT 0202 increased the doses of PTZ required to induce clonic and tonic convulsions, as well as death. In the electroconvulsive shock test, EHT 0202 significantly increased the current threshold for inducing tonic convulsions and in the psychomotor seizure (6 Hz) model in the mouse, EHT 0202 significantly decreased the forelimb seizure score. Furthermore, the compound's neuroprotective effect against excitotoxic stresses suggests that it could also be active against epileptogenesis. EHT 0202 does not trigger side effects typically exhibited by drugs targeting the GABAA receptor, in particular sedation (3).

Studies are ongoing to select a lead compound for the EHT 207 program that displays a strong therapeutic potential in epilepsy and a good safety profile.

About Epilepsy

Epilepsy is a chronic brain disorder that affects people of all ages. It is characterized by recurrent seizures - which are physical reactions to sudden, usually brief, excessive electrical discharges in a group of brain cells. Seizures can vary from the briefest relapses of attention or muscle jerks, to severe and prolonged convulsions. Seizures can also vary in frequency, from less than one per year to several per day. Epilepsy increases a person's risk of premature death by about two to three times compared to the general population.

The World Health Organization estimates that 50 million people worldwide suffer from epilepsy.

Antiepileptic drugs are not effective in about 30% of the treated patients (4).

About ExonHit Therapeutics

ExonHit Therapeutics (Alternext: ALEHT) is a fast emerging healthcare player active in both therapeutics and diagnostics. The Company is applying its proprietary technology, based on the analysis of alternative RNA splicing, to develop diagnostic tests and innovative treatments for neurodegenerative diseases, especially Alzheimer's disease, and cancers. ExonHit has a balanced investment strategy with internal development programs and strategic collaborations, in particular with bioMérieux and Allergan.

ExonHit is headquartered in Paris, France and has a U.S. facility in Gaithersburg, Maryland. The Company is listed on Alternext of NYSE Euronext Paris. For more information, please visit http://www.exonhit.com.

Disclaimer

This press release contains elements that are not historical facts including, without limitation, certain statements on future expectations and other forward-looking statements. Such statements are based on management's current views and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those anticipated.

In addition, ExonHit Therapeutics, its shareholders, and its affiliates, directors, officers, advisors and employees have not verified the accuracy of, and make no representations or warranties in relation to, statistical data or predictions contained in this press release that were taken or derived from third party sources or industry publications, and such statistical data and predictions are used in this press release for information purposes only.

Finally, this press release may be drafted in the French and English languages. In an event of differences between the texts, the French language version shall prevail.

References

(1) Maksay G, Ticku MK. Dissociation of [35S]t-butylbicyclophosphorothionate binding differentiates convulsant and depressant drugs that modulate GABAergic transmission. J Neuroch. 1985 Feb; 44(2):480-6

(2) Pellow S, File S. Pro- and anti-convulsant drug effects in combination with the convulsant benzodiazepine Ro 5-4864. J Pharm Pharmacol 1985; Aug,01;37(8):560-3

(3) In house data

(4) http://www.who.int/mediacentre/factsheets/fs999/en/print.html

Source
ExonHit Therapeutics