Tang, B.; Ghosh, D.; Hoss, W.; Messer, W. Stimulation of a-secretase and Akt by the muscarinic agonist CDD-0102, Society for Neuroscience, Annual Meeting, Poster #296.13, 2003.

Messer, W.S., Jr., K.A. Bachmann, C. Dockery, A.A. El-Assadi, E. Hassoun, N. Haupt, B. Tang and X. Li. Development of CDD-0102 as a selective M₁ agonist for the treatment of Alzheimer’s disease. Drug Dev. Res. 57(4): 200-213, 2003.

Cao, Y., M. Zhang, C. Wu, S. Lee, M.E. Wroblewski, T. Whipple, P.I. Nagy, K. Takács-Novák, A. Balázs, S. Tőrös and William S. Messer, Jr. Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. J. Med. Chem. 46:4273-4286, 2003.

Messer, W.S., Jr., Cholinergic agonists and the treatment of Alzheimer’s disease. Curr. Top. Med. Chem. 2: 353-358, 2002.

Messer, W.S., Jr., The utility of muscarinic agonists in the treatment of Alzheimer’s disease. J. Mol. Neurosci. 19: 187-193, 2002.

Rajeswaran, W.G., Y. Cao, X.-P. Huang, M.E. Wroblewski, T. Colclough, S. Lee, F. Liu, P.I. Nagy, J. Ellis, B.A. Levine, K.H. Nocka and W.S. Messer, Jr. Design, synthesis and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. J. Med. Chem. 44(26): 4563-4576, 2001.

Messer, W.S., Jr., W.G. Rajeswaran, Y. Cao, H.-J. Zhang, A.A. El-Assadi, C. Dockery, J. Liske, J. O’Brien, F.E. Williams, X.-P. Huang, M.E. Wroblewski, P.I. Nagy and S.M. Peseckis. Design and development of selective muscarinic agonists for the treatment of Alzheimer’s disease: Characterization of tetrahydropyrimidine derivatives and development of new approaches to improved affinity and selectivity for M₁ receptors. Pharm. Acta Helv 74(2-3): 135-140, 2000.

Messer, W.S., Jr., Y.F. Abuh, Y. Liu, S. Periyasamy, D.O. Ngur, M.A.N. Edgar, A.A. El-Assadi, S. Sbeih, P.G. Dunbar, S. Roknich, T. Rho, Z. Fang, B. Ojo, H. Zhang, J.J. Huzl, III and P.I. Nagy. Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives as selective m1 agonists. J. Med. Chem. 40: 1230-1246, 1997.

Messer, W.S., Jr., Y.F. Abuh, K. Ryan, M.A. Shepherd, M. Schroeder, S. Abunada and A.A. El-Assadi. Tetrahydropyrimidine derivatives display functional selectivity for M₁muscarinic receptors in brain. Drug Dev. Res. 40: 171-174, 1997. 

Issued US Patents

5,175,166 – December 29, 1992
5,403,845 – April 4, 1995
5,618,818 – April 8, 1997
5,726,179 – March 10, 1998
6,096,767 – August 1, 2000
6,211,204 – April 3, 2001
6,369,081 – April 9, 2002
6,376,675 – April 23, 2002
6,602,891 – August 8, 2003

Issued Foreign Patents

Austrian Patent No. 187070
European Patent No. 0630244 – 1999
German Patent No. 69230378.2
Japanese Patent No. 3,411,276 – 2003
Spanish Patent No. 2138977

Board of Directors:
The three members of the management team and Debasis Ghosh, Ph.D., a co-founder and former President of Cognitive Pharmaceuticals, Ltd., constitute the Board of Directors. Dr. Ghosh has extensive experience in the discovery and development of medicinal agents for the treatment of brain disorders and cancer.

Scientific Advisory Board:
A Scientific Advisory Board has been established and a number of national and international experts are currently being recruited. Current members include:

- Graham Durant, Ph.D., Co-inventor of Tagamet and CDD-0102
- Paul Erhardt, Ph.D., Inventor of Esmolol, Professor, Universty of Toledo
- Chandramallika Ghosh, Ph.D., Head, In Vitro Toxicology, NAMSA
- Kenneth Bachmann, Ph.D., Distinguished Professor, University of Toledo
- John Kasckow, MD, Ph.D., Director of Geriatric Psychiatry, University of Cincinnati & Virginia

Funding:
Basic research underlying the RBDD technology was sponsored by grants, primarily to the University of Toledo, from pharmaceutical companies, the NIH, and a private foundation. Total expenditures on discovery and development thus far are in excess of $2.5 million. An additional $2.5 million will be required to complete pre-clinical toxicology studies and the manufacturing of CDD-0102, supporting an IND in 2005. The management team believes that the project has the potential for significant return on investment within a reasonable time frame.

Our History:
Cognitive Pharmaceuticals was established in 2001 based on a proprietary platform technology developed at the University of Toledo, College of Pharmacy. In April 2003, Cognitive Pharmaceuticals was registered in Michigan as a for-profit organization [www.medc.michigan.org] [www.michbio.org]. Emphasis is on products with significant return on investment in expanding markets with unmet needs.

A potential treatment of Alzheimer’s disease, a debilitating brain disorder, is presently in development. The mechanism of action of CDD-0102 differs from marketed drugs, targeting both the symptoms – progressive loss of memory and cognitive function – and the underlying cause of the disease – accumulation of amyloid plaque and neurofibrillary tangles. Pharmacodynamic investigation with CDD-0102 demonstrate efficacy in vitro and in an animal model of Alzheimer’s disease. The current focus is the completion of preclinical safety studies with the intention of filing an Investigational New Drug Application (IND) with the Food and Drug Administration (FDA).

The proprietary platform technology – Receptor Based Drug Design (RBDD) – has thus far resulted in nine issued US patents and foreign equivalents. CDD-0304 is presently being investigated for its potential role in alleviating memory and cognitive deficits and behavioral disturbances associated with Alzheimer’s disease and schizophrenia. Additional patent applications are being prosecuted, a number are in preparation. Potentially, this technology will yield additional products, including new approaches in the treatment of pain and addiction.