French company ExonHit Therapeutics has reported encouraging progress in a Phase II trial with EHT 0202, its lead product candidate for Alzheimer’s disease.

ExonHit applies alternative RNA splicing technology to the development of diagnostic tests and treatments for neurodegenerative diseases and cancer.

It says EHT 0202 has a novel mechanism of action compared with existing therapies for Alzheimer’s, in that the compound stimulates the _-secretase pathway, thereby enhancing production of the procognitive and neuroprotective sAPP_ fragment of Amyloid Precursor Protein.

“Since the stimulation of the _-secretase pathway is to the detriment of A_ amyloid peptide production, EHT 0202 potentially reduces toxic A_ plaque formation,” ExonHit explains.

In the top-line Phase IIa data presented at the 13th Congress of the European Federation of Neurological Societies in Florence, Italy, EHT 0202 was shown to be safe at both tested doses (40mg and 80mg twice daily) and to be generally well tolerated. The most frequent adverse events were mainly related to the compound’s action on the central nervous system and were dose-dependent, ExonHit noted.

There were also some signs of cognitive improvement, as measured by the gold-standard ADAS-Cog test, in patients treated with EHT 0202, the company reported. Moreover, in some assessments (including ADAS-Cog), it was observed that the ApoE4-positive subpopulation – patients with one or two of the ApoE4 alleles in their genes – tended to respond better to EHT 0202 than ApoE4-negative patients.

These various benefits “support advancing EHT 0202 into later-stage clinical development to collect further evidence of safety and efficacy in a larger number of patients and over a longer time period”, commented lead investigator Professor Bruno Vellas. “There is a high unmet need for new Alzheimer treatments with precognitive and neuroprotective properties.”

ExonHit said it would now actively seek out a partner to ensure rapid clinical development and commercialisation of EHT 0202.

The Phase IIa study was conducted in 23 centres across France and involved a total of 197 ambulatory patients aged 60-90 years and with mild to moderate Alzheimer’s disease. Of the total, 159 were randomised to receive either oral treatment with EHT 0202 as adjunctive therapy to an acetylcholinesterase inhibitor or placebo over a three-month period.