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CoMentis Announces Proof-of-Activity Data From Its Phase I Study of Disease-Modifying Alzheimer's Disease Therapy

Posted on: Monday, 7 January 2008, 18:00 CST

CoMentis, Inc., a privately held biopharmaceutical company, announced today that it has completed a Phase I study of its proprietary, orally bioavailable, small-molecule beta-secretase inhibitor, CTS-21166, which is being developed as a disease-modifying treatment for Alzheimer's disease. Results from the study indicate that CTS-21166 is safe and well-tolerated. 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 predose levels. The top doses of CTS-21166 further demonstrated a sustained reduction in AUC that was greater than 40% over 72 hours.

"These data represent a significant advancement in the development of novel therapeutics to treat Alzheimer's disease. CTS-21166 produced a rapid and significant reduction of plasma amyloid beta, a key biomarker that is believed to be involved in the pathogenesis of Alzheimer's disease," stated Henry Hsu, M.D., CoMentis Chief Medical Officer. "CTS-21166 represents an entirely new approach to the treatment of Alzheimer's disease by inhibiting beta-secretase, an enzyme critical in the production of potentially toxic amyloid beta. It has the potential to become the first-in-class disease modifying therapeutic agent."

The Phase I trial in healthy volunteers 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.

"We are very excited about the potential of our beta-secretase inhibitor platform and we anticipate launching a Phase II study of oral CTS-21166 in Alzheimer's patients in 2008," said W. Scott Harkonen, M.D., CoMentis President and Chief Executive Officer. "In an effort to accelerate the development of this platform, we are in advanced partnership negotiations with multiple parties and we expect to complete a transaction during the first quarter of 2008."

Beta-Secretase and Alzheimer's Disease

Drs. Jordan Tang and Arun Ghosh, two of the scientific founders of CoMentis, are pioneers in the field of aspartic proteases. Since publication of the first beta-secretase inhibitor in 2000, Dr. Tang has led the characterization of this enzyme's role in Alzheimer's disease and Dr. Ghosh has led the construction of drug candidates to inhibit its activity. The action of this enzyme on the amyloid precursor protein leads to the formation of plaques in the brain and is implicated in the development of Alzheimer's disease. Inhibition of beta-secretase reduces amyloid beta production and could slow the progression of Alzheimer's disease. CTS-21166 is the first of several highly selective, potent and orally active beta-secretase inhibitors being developed by CoMentis that show excellent efficacy in preclinical models of Alzheimer's disease.

"This is the most exciting target today for intervention in the pathogenesis of Alzheimer's disease," said Dr. Tang, who holds the J.G. Puterbaugh Chair in Medical Research at the Oklahoma Medical Research Foundation. "Beta-secretase is involved at a very early stage in the disease, and if we could block the activity of this enzyme, we could prevent many of the harmful steps that follow and drastically reduce the impact of Alzheimer's disease."

About CoMentis

CoMentis, Inc. has its headquarters in South San Francisco, with research operations in both South San Francisco and Oklahoma City. The company is engaged in the discovery and development of small-molecule drugs to treat Alzheimer's disease, age-related macular degeneration (AMD) and cognitive disorders. The company has two fundamental technology platforms: (i) aspartic protease inhibitors, including beta-secretase inhibitors for Alzheimer's disease; and (ii) nicotinic acetylcholine receptor (nAChR) agonists and antagonists for the treatment of angiogenesis mediated diseases and cognitive disorders.

Originally founded in 2004 as Athenagen, Inc., the company was re-named CoMentis following the August 2006 merger with Zapaq, Inc., which created a leading neurovascular disease franchise. Zapaq was founded in 2001 by Jordan Tang, Ph.D., of the Oklahoma Medical Research Foundation, and Arun Ghosh, Ph.D., now at Purdue University, both experts in the field of aspartic proteases. Dr. Tang's groundbreaking discovery of beta-secretase, an aspartic protease which is a critical enzyme in beta amyloid production, was published in Proceedings of the National Academy of Sciences in 2000.

CoMentis currently has three product development programs based on its two technologies: ATG-3, a topical (eye drop) anti-angiogenesis compound for neovascular AMD; CTS-21166, an orally active beta-secretase inhibitor for Alzheimer's disease; and GTS-21, an oral agonist of the alpha-7 nACh receptor pathway for cognition enhancement. For more information: www.comentis.com.

 CONTACT: W. Scott Harkonen, M.D. President and CEO (650) 869-7600 Email Contact

SOURCE: CoMentis, Inc.

Source: MARKET WIRE

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