Alzheimer’s disease

Alzheimer’s disease affects approximately 5.1 million Americans, and that number is expected to increase by 50% by 2030. Current therapies for Alzheimer patients provide only mild, transient symptomatic relief. There is a significant unmet need for improved drugs that can modify the underlying course of disease. Over $4 billion in revenues are currently generated by four drugs.

CTS-21166, a proprietary, orally bioavailable, small-molecule beta-secretase inhibitor, is being developed as a disease-modifying treatment for Alzheimer’s disease (AD). In preclinical studies, CTS-21166 exhibits excellent efficacy, selectivity, brain penetration and pharmacologic activity.

CoMentis successfully completed a Phase I study of CTS-21166 in healthy volunteers in the first quarter of 2008. Results indicated that CTS-21166 was safe, well-tolerated and pharmacodynamically active at all dose levels.

The trial was designed as a dose escalation study to assess the safety, tolerability and pharmacokinetics and pharmacodynamics of CTS-21166 following intravenous administration. Forty-eight subjects received one of six different doses or placebo. The study measured levels of CTS-21166 and levels of amyloid beta in the plasma. CTS-21166 demonstrated excellent pharmacokinetic properties including dose proportional exposure and very low inter-subject pharmacokinetic variability. In addition, the pharmacokinetic profile is consistent with once a day dosing and will support a commercial product.

Pharmacodynamic proof of activity was achieved as subjects displayed a robust, sustained and dose-related reduction in plasma amyloid beta in both area-under-curve (AUC) reduction and peak reduction with effects lasting over 72 hours. Single dose administration of CTS-21166 produced a greater than 60% reduction of plasma amyloid beta measured either by AUC over 24 hours or as a maximal reduction relative to pre-dose levels. The top doses of CTS-21166 further demonstrated a sustained reduction in AUC that was greater than 40% over 72 hours.



In addition to CTS-21166, CoMentis has an expansive portfolio of back-up and next generation beta-secretase inhibitor compounds in various stages of pre-clinical development.