BPS 2016
Development of a Novel Peptide Therapeutic for Treatment of Frontotemporal Dementia (FTD)
Yvonne Angell
Scientific Consultant, Cogentis Therapeutics
ABSTRACT
Cogentis is a pre-clinical stage biotechnology company dedicated to developing therapies that target the dysregulated cyclin-dependent kinase 5 (CDK5) molecular pathway. Because clinical trials for Alzheimer’s disease (AD) are costly and slow, Cogentis will focus initially on frontotemporal dementia (FTD), a rare disorder that is an early-onset, rapidly-progressive neurodegenerative condition leading to death within five years. FTD and AD are thought to be tauopathies, diseases characterized by toxic accumulations of a normal protein called ‘tau’ in the brain. There are currently no approved drugs to treat any of the tauopathies. In brains from FTD patients CDK5 over-phosphorylates tau, leading to the toxic accumulation of tau. Post-mortem brains from AD and FTD patients were shown to have elevated CDK5 activity. Previous efforts to inhibit CDK5 have proven too toxic due to lack of specificity. Cogentis has exclusive rights to CT-526, a novel peptide which was invented at the NIH and is an allosteric CDK5 inhibitor. CT-526 penetrates the blood-brain barrier and engages CDK5 away from the active site, preventing aberrant activity while preserving normal function, showing zero signs of toxicity at > 100x the effective dose. Preclinical success in multiple mouse models of AD, Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) supports expansion/development to multiple diseases. In advanced AD mice, it reversed tau phosphorylation, amyloid beta plaques (Ab), motor instability and cognitive deficits to normal.
BIO
For the past 20 years my career has focused on the discovery and development of new peptide therapeutics in a wide range of disease areas, including oncology, endocrinology, hematology and neurology. I have built a strong reputation in the peptide therapeutics field by leading successful chemistry teams and research programs in small biotech companies, mid-size and large pharmaceutical companies. My main expertise is in the design, synthesis and lead optimization of novel, challenging peptides and peptidomimetics, peptide-conjugate linker design and synthesis, unnatural amino acid and building block synthesis, peptide PEGylation and lipidation, formulation and CMC activities. I have influenced the strategic direction to advance many drug discovery programs including three drug candidates in preclinical development, one in the market, and one in phase I clinical trials.