BioWorld International Correspondent

PARIS - ExonHit Therapeutics SA reported that the Phase III trial of Ikomio, its drug candidate for amyotrophic lateral sclerosis (ALS), failed to attain its primary efficacy endpoint of survival at 18 months.

The drug did not demonstrate any benefit in that respect compared to placebo. The trial was conducted at 12 centers around Europe, and the 400 patients received Ikomio (or placebo) in addition to Rilutek, the only approved treatment for ALS, during the 18-month period.

CEO of Paris-based ExonHit, Bruno Tocqué, told BioWorld International that the outcome "certainly does not strengthen our technological platform," but that the company still had confidence in it and that it would not alter the company's business strategy. He confirmed that the next product in ExonHit's pipeline, EHT 0202, a treatment for Alzheimer's disease that is nearing the end of a Phase I trial, will be taken into Phase II around the middle of 2005.

Ikomio is a formulation of pentoxifylline, a drug used to treat certain cardiovascular conditions, and events since the beginning of 2004 seemed to validate ExonHit's decision to develop it for ALS. In January, the independent Data Safety Monitoring Board recommended that ExonHit continue its development of the product, having concluded that there were no safety concerns. Then, in June, ExonHit announced that it had developed an improved formulation of Ikomio based on microgranules that would ensure a more controlled release of the active ingredient and make the drug easier to swallow.

That is the formulation that ExonHit intended to commercialize, and the company produced an initial batch of 200 kilos for carrying out a bioequivalence study to compare it with the non-microgranule formulation used in the Phase III trial. That study will not be carried out now, and Tocqué said Ikomio would be abandoned since it had no other potential applications. ExonHit had talked of filing the drug for regulatory approval in Europe as early as the first half of 2005.

ExonHit is engaged in the development of both therapeutics and diagnostics using its qualitative gene-profiling technology, DATAS (Differential Analysis of Transcripts with Alternative Splicing). That technology detects relevant changes in mRNA sequences resulting from alternative RNA splicing without high-throughput sequencing, and ExonHit derives value from it by making it available to third parties.

Its therapeutics programs are designed to generate validated "ready-for-development compounds" (RDCs) for licensing out to third parties. The company focuses on two types of pathology - neurodegenerative diseases and cancer. It has two additional products in preclinical development: EHT 0101, its leading cancer drug, and EHT 0204, another product emanating from its neurodegenerative program.

ExonHit plans to initiate a Phase I trial of one in 2005, since, as Tocqué said, the company does not have the resources to start clinical development of both right away. He added that the company had four other new chemical entities in preclinical development.

In toxicology, ExonHit's flagship product is Safe-Hit, a microarray-based system for evaluating and ranking compounds for toxicity. Only last week it signed a site-license agreement for Safe-Hit with Tokyo-based Mitsubishi Pharma Corp. In addition, ExonHit is developing a prostate cancer diagnostic test based on alternatively spliced isoforms, as well as a blood-based diagnostic test for colon cancer.

Tocqué confirmed that the company had funding to continue its activities for another two years, having raised €8.3 million (US$10.2 million) from existing shareholders and their affiliates in February through an issue of convertible bonds that can be exchanged for shares in mid-2006. Since it was founded in 1997, the company has raised a total of €55.3 million in three funding rounds.

Another funding round might be necessary in 2006, Tocqué said, depending on the revenues ExonHit is generating from research collaborations and license agreements. In 2003 its revenues amounted to €5.4 million, but Tocqué declined to speculate on whether the figure would be higher in 2004, saying it would be affected by exchange-rate movements. He also indicated that ExonHit's ambitions for launching an initial public offering would have to be put back two years as a result of the setback with Ikomio.

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