BioWorld International Correspondent

PARIS - ExonHit Therapeutics SA has embarked on its first clinical trial, a Phase II study that will test its lead compound, EHT 0201, in the treatment of amyotrophic lateral sclerosis.

The trial will take place in 12 centers in Europe and will evaluate the safety and efficacy of a therapy combining EHT 0201 with Rilutek (riluzole) for treating ALS patients.

ALS (also known as motor neuron disease, Charcot's disease or Lou Gehrig's disease) is a fatal disease for which there is no cure and no proven therapy for preventing or reversing its development. Rilutek (produced by the Franco-German pharmaceutical company Aventis SA) is the only drug currently approved for treating the disease and it does no more than delay death for a few weeks, ExonHit said.

EHT 0201 is a formulation of pentoxifylline, a drug that already is on the market for the treatment of certain cardiovascular conditions. Its potential for the treatment of ALS was discovered by ExonHit using its proprietary gene-profiling technology, DATAS (differential analysis of transcripts with alternative splicing). Applying DATAS to animal models of ALS, ExonHit detected different tissue-specific RNA isoforms that are produced as a result of splicing alterations that occur during the onset of the disease.

That information enabled it to identify a number of potential new therapeutic targets at work in the presymptomatic stage of the disease model. EHT 0201 was selected for clinical development from a library of compounds following an evaluation of its pharmacological effects (including comparisons with riluzole) against a subset of the new molecular targets.

ExonHit's CEO, Bruno Tocqué, told BioWorld International that the company was confident in EHT 0201's therapeutic potential as a single treatment for ALS, given that its development was based on a better understanding of the molecular cause of the disease, but that for ethical reasons it was decided to test it first in combination with the only drug currently available to treat the disease.

The decision to take EHT 0201 straight into a Phase II trial to evaluate it directly in patients suffering from ALS reflects what ExonHit calls the compound's "already well-characterized safety profile." Tocqué stressed that this was one of the first examples of genomics' contribution to speeding up the drug discovery process.

"By moving from target identification to Phase II trials in less than one year, we have clearly demonstrated the value of our DATAS technology in progressing drug candidates into the clinic much faster than the industry norm," he said.

The 12 centers (four in France, four in the UK, three in Germany and one in Belgium) will recruit up to 400 patients and conduct a double-blind, placebo-controlled study entailing the administration of EHT 0201 in combination with Rilutek. The trial will last more than 18 months and the first results are expected toward the end of 2004.

EHT 0201 is one of four compounds that ExonHit has under development. Of the other three, one, EHT 0202, also is designed to treat ALS, while the other two, EHT 0101 and EHT 0102, are for cancer.