Treventis AD diagnostic tested in mice
Research presented this year at the Alzheimer’s Association International Conference® (AAIC®), the world’s largest forum…
There is a large and rapidly growing unmet need for disease modifying drugs for Alzheimer’s disease. In 2015, the Alzheimer’s Association estimated that there were 5.3 million Americans with Alzheimer’s disease; by 2050 they estimate that this number will triple to 13.8 million. It is the sixth-leading cause of death in the industrialized world – and there is no cure.
Alzheimer’s disease pathology includes “plaques” of beta-amyloid and “tangles” of tau protein. These proteins tend to abnormally “clump”, and such protein misfolding processes give rise to inflammation and neuronal death. In order to make an impact on this disease, drugs must be found that can potently and selectively stop this process.
Because amyloid proteins fold into various conformations and are generally disordered, it has been impossible to develop crystal structures to support rational drug design. Treventis scientists identified a common binding site based on epitope commonality between multiple misfolded amyloids. This information was used to build an experimentally validated model of the earliest stage of misfolding: a proprietary, patent-pending system known as “common conformational morphology” (CCM).
Using CCM, we can digitally screen, identify, and optimize numerous classes of potent, drug-like compounds before making and testing them experimentally – making structure-based design a reality for anti-amyloid drug discovery.
In collaboration with the Wellcome Trust, we have successfully developed lead compounds that have potent effects on both beta-amyloid and tau protein in vitro, are brain-penetrant, and are well tolerated in oral dosing. We have recently shown significant effects on amyloid levels in vivo with our dual-action lead compound. Candidate selection is ongoing and we expect to begin IND studies in 2017.
Our discovery platform can identify compounds that potently block the progression of amyloid toxicity. These compounds can be designed with selectivity toward a particular amyloid or with polypharmocology, for proteins implicated in over 30 rare/orphan diseases and major indications including
Dr. Barden, a registered patent agent and computational scientist, has over ten years of experience in drug discovery management. A veteran of programs in the neurodegenerative and anti-infective spaces, he developed the Company’s virtual high-throughput screening library (>11 million compounds) and is a key architect of our proprietary “CCM” model of protein misfolding. Dr. Barden received his Ph.D. in Physical Chemistry from the University of Georgia.
Dr. Reed has recently held a Senior Research Scientist position within the medicinal chemistry group at Schering-Plough Corporation, specializing in the area of oncology. Prior to this post, Dr. Reed spent 3 years as a medicinal and process chemist at a large biotechnology company, ICOS Corporation, where he gained experience in the area of inflammation, anti-infectives and oncology. Prior to his recent industrial career, Dr. Reed carried out extensive post-doctoral training within one of the top synthetic organic chemistry research groups in the world, where he developed novel synthetic methodology, obtained several publications and co -wrote a successful $10 million research grant (CFI). He received his B.Sc. with honors from University of Reading (UK) and his Ph.D. in organic chemistry from the University of Sussex (UK).
Dr. Taylor heads up a team of researchers working to develop screening tools for amyloid drug discovery, including proof of concept and mechanism of action studies. A variety of biophysical, biochemical, cell-based, and in vivo tests are being developed in house and in collaboration with other scientists worldwide. Prior to joining Treventis, Dr. Taylor led the biology program at DeNovaMed, a Halifax, Nova Scotia based company developing novel anti-infectives. Dr. Taylor was awarded her PhD in Biochemistry and Molecular Biology from Dalhousie University, Canada, followed by postdoctoral training in Biochemistry at the University of Geneva, Switzerland.
Dr. Weaver is Director of the Krembil Research Institute and Professor in the Departments of Medicine, Chemistry and Pharmacy at the University of Toronto. He has published over 150 peer-reviewed articles and is an inventor on over 70 patents. In addition to being a practicing neurologist Dr. Weaver is a recognized expert in computer-aided drug design. Dr. Weaver’s work in the fields of quantum and molecular mechanics to design drugs through the use of high throughput in-silico screens has been instrumental in his founding of several biotech companies. Most notably at Neurochem Inc. Dr. Weaver discovered and developed tramiprosate (Alzhemed), the first “disease modifying” small molecule anti-amyloid aggregation drug in the world to reach phase 3 clinical trials for the treatment of Alzheimer’s Disease. Following an IPO, Neurochem was publicly traded on the Toronto Stock Exchange and NASDAQ. Dr. Weaver is the recipient of numerous grants, awards and honors a selection of which include the 2011 Jonas Salk Award, 2010 Bantrel Award, 2009 Prix Galien (for research into the cause of Alzheimer’s Disease) and the 2003 Queen Elizabeth II Jubilee Medal. Dr. Weaver is the past President of Epilepsy Canada. He received his M.D. and Ph.D. degrees from Queen’s University in Kingston, Ontario, Canada.
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