Novel Therapeutics Derived from Company’s Proprietary Stem Cell Capabilities
SOUTH SAN FRANCISCO, Calif.-- iPierian, Inc., announced today the first development programs in its drug pipeline: monoclonal antibodies to treat neurodegenerative diseases by targeting the Tau protein and the Complement pathway. Tau protein and the Complement pathway represent central mechanisms driving an array of neurodegenerative diseases, which will allow the company to pursue a series of disease indications.
The emergence of the two development programs in Tau and Complement follow from iPierian’s decision to focus its drug discovery programs exclusively on neurodegenerative diseases, an area where access to patient brain tissue for study remains elusive. The company plans to advance both the Tau and Complement programs internally in parallel.
“iPierian’s platform provides a unique approach to neurodegenerative disease drug development, incorporating human disease biology at the very beginning of the discovery process,” said Nancy Stagliano, PhD, CEO of iPierian. “Our recent insights derived from human iPSCs have encouraged us to quickly move our Tau and Complement programs forward. iPierian’s patient-derived models of neurodegeneration and neuroinflammation are allowing us to realize the promise of iPSC technology in a very product-oriented way.”
The monoclonal antibody development programs evolve from iPierian’s research utilizing the company’s know-how in disease modeling of patient-derived induced pluripotent stem cells (iPSCs). The disease models, which combine human cortical neurons, motor neurons, microglia, and astrocytes in a dish, are used by iPierian to discover and validate novel therapeutic targets or mechanisms of disease. Leveraging the company’s iPSC capabilities can provide insight into the earliest drivers of diseases such as Alzheimer’s, in contrast to conventional autopsy samples which typically only allow for study of end-stage pathophysiology.
iPierian’s approach using iPSCs offers a distinctive angle into the importance of Tau in specific patient populations. By studying the role of Tau in human cells, the company aims to advance a novel therapeutic into the clinic for multiple tauopathies (Alzheimer’s disease, Frontotemporal Dementia, Progressive Supranuclear Palsy (PSP) and others). In targeting the Complement cascade in the innate immune system, iPierian’s platform is being leveraged to tease out specific mechanisms of chronic inflammation that occur in various brain disorders.
The Tau protein functions to stabilize microtubules and is abundant in neurons in the central nervous system. Aberrantly modified forms of tau have been correlated with dementias such as Alzheimer’s disease (AD), Frontotemporal Dementia, PSP, and other tauopathies. Aberrant Tau accumulation correlates with the disease progression of dementia, in contrast to Amyloid β which maximally deposits years prior to dementia and therefore may be too late to intervene against. Animal models of AD have recently suggested that Tau can spread from one neuron to another, transmitting pathological Tau and correlating with the progression of AD pathology in humans. It is possible that therapeutics which slow the spread of Tau may also slow the clinical course of AD and related tauopathies.
The complement system consists of a family of distinct proteins that play a pivotal role in host defense against infection, as well as facilitating phagocytosis by macrophages/microglia and promoting inflammation. Many inflammatory, autoimmune, and infectious diseases have been shown to be associated with excessive complement activity. Complement activation has also been associated with several neurodegenerative diseases – including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Genome wide association studies have identified polymorphisms in genes encoding components of the Complement pathway as risk factors for Alzheimer’s disease.