Analyses of tramiprosate Phase 3 trials show improvement in cognition and function in APOE4 positive alzheimer’s disease subjects reaching 4 point improvement from placebo on ADAS-cog in homozygous APOE4 subjects, and support development of ALZ-801, a novel prodrug of tramiprosate with optimized drug properties

Presented at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases in Nice, France.

J.A. Hey, M. Versavel, J. Sampalis*, J.Y. Yu, P.H. Reinhart, J. Cummings**, Miia Kipivelto***, M. Bairu**** and M. Tolar

Alzheon Inc., Lexington, MA, USA,*JSS Medical Research, Inc., St. Laurent, QC Canada, **Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Nevada and Cleveland, USA, ***Karolinska Institutet Alzheimer Disease Research Center, Stockholm, Sweden, and ****Serenus Biotherapeutics, Inc., San Francisco, CA, USA.

ALZ-801 is a novel, orally available small molecule prodrug of tramiprosate with improved pharmaceutical properties. ALZ-801 has an improved oral absorption profile, gastrointestinal tolerability and pharmacokinetic properties. Compared with oral tramiprosate in a single dose Phase 1 study, ALZ-801 pharmacokinetic variability was reduced by ~50% with an extended terminal t1/2 of 14.9 hours, allowing once-daily dosing. Oral tramiprosate was advanced to a 2,000 patient Phase 3 program which completed in 2007 with inconclusive results due to Alzheimer’s disease misdiagnosis, which reached ~30% of the subjects. Post-hoc analyses of subjects with at least one ε4 allele of apolipoprotein E gene (ApoE4 positive) in the North American Phase 3 study (n=599), showed that tramiprosate produced a clinically meaningful improvement in cognition (ADAS-cog) and function (CDR-SB) through 18 months, on top of treatment with acetylcholinesterase inhibitors and/or memantine (tramiprosate 150 mg BID, n=183; ADAS-cog: slope vs. placebo p<0.01, and p