Prothena Corporation plc (Nasdaq: PRTA) is a clinical-stage biotechnology company discovering and developing novel monoclonal antibodies that are directed towards misfolded proteins or improper cell adhesion.
The Company’s work in protein misfolding could result in therapies to treat several neurodegenerative diseases, including AL (primary) and AA (secondary) forms of amyloidosis (NEOD001), Parkinson's disease and related synucleinopathies (PRX002). Prothena’s novel cell adhesion development activities could generate new therapies to treat inflammatory diseases and metastatic cancers (PRX003). Our strategy is to identify antibody candidates for clinical development by applying Prothena’s extensive expertise in generating novel therapeutic antibodies and working with collaborators having expertise in specific animal models of disease. Our lead program, NEOD001, is in Phase 1, and we anticipate moving one or more of our product candidates into clinical development each year in 2014 and 2015.
Prothena has attracted an elite team with a recognized track record both for profound scientific discoveries and for the development of therapeutics that have become leading commercial products in their respective therapeutic categories. The team brings this heritage to Prothena with the vision of continuing to create and develop novel antibody-based therapies that benefit a diverse population of patients. We also have assembled a globally recognized Scientific Advisory Board with a broad spectrum of academic and industry experience in the fields of neuroscience and immunotherapy.
Prior to December 2012, the Prothena Business operated as part of Elan Corporation, plc (Elan), not as a separate stand-alone entity. Prothena’s business consists of a substantial portion of Elan’s former drug discovery business platform, including Neotope Biosciences Limited and Onclave Therapeutics Limited, each former wholly owned subsidiaries of Elan. After the separation from Elan and the related distribution of our ordinary shares to Elan’s stockholders, our ordinary shares began trading on The NASDAQ Global Market under the symbol “PRTA” on December 21, 2012.
Prothena is targeting proteins in novel ways to resolve unmet medical needs in patients.
The history of Prothena began with Athena Neurosciences, which was founded in 1986. Since Athena’s inception, the company’s scientists consistently have made significant discoveries that have advanced our understanding of the biology of Alzheimer’s disease. Particularly impactful were the fundamental breakthroughs we made in elucidating the roles amyloid, gamma secretase, and beta secretase play in the disease. These discoveries led to the development of a drug discovery and development organization, which generated multiple clinical candidates that have been and continue to be tested in Alzheimer’s disease patients.
These same scientists also pioneered significant scientific discoveries with cell adhesion molecules, leading to the discovery and development of Tysabri® (natalizumab), which is now approved for use in relapsing forms of multiple sclerosis and sold by Biogen Idec.
Athena was acquired by Elan Corporation in 1996, and its discovery and development activities were incorporated into Elan Pharmaceuticals at that time. In December 2012, Elan completed the successful demerger of its discovery and early development efforts resulting in Prothena, which is an independent publicly traded company with a strong pipeline of discovery programs, early stage clinical assets and preeminent scientists.
Instead of focusing on a specific therapeutic indication or platform technology, Prothena focuses on what we are best at – elucidating the contribution of protein misfolding and cell trafficking dysfunction to disease states and developing therapeutic approaches that interact in novel ways with proteins. Today, we are building a broad pipeline of compounds that could deliver the next generation of breakthrough therapies by drawing from our vast knowledge of in these areas of biology.
Amyloidosis is a term used for a variety of conditions that result when a normally soluble protein misfolds and accumulates, which can become toxic to organ tissue. Amyloidoses can affect any organ in the body, including the brain and peripheral organs. For example, the misfolding and aggregation of the amyloid beta (Aβ) peptide leads to a build-up of amyloid protein in the brain, which most scientists believe is the primary cause of Alzheimer’s disease. The scientific discoveries the team has made in Alzheimer’s disease led to the discovery of potential methods for intervening in the amyloidosis that occurs in other parts of the body. Amyloidogenic proteins including amyloid light chain (AL), amyloid A (AA) and transthyretin (TTR) are believed to cause toxicity in peripheral organs under pathological conditions. Collectively, the peripheral diseases caused by these proteins are known as systemic amyloidoses.
Our goal is to develop new product candidates that target these misfolded proteins, and our lead candidate, NEO001, has begun Phase 1 clinical testing in AL amyloidosis patients.
Synucleins are a family of proteins, of which there are three known members: α-synuclein, β-synuclein, and ?-synuclein. The α- and β-synuclein proteins are found primarily in brain tissue. The ?-synuclein protein is found primarily in the peripheral nervous system and retina, as well as several tumor types. While the role synuclein proteins play in normal cellular functioning has not been fully determined, there are data to suggest that synucleins assist with the stability of cellular membranes and/or their turnover.
Mutations and changes in the levels of α-synuclein have been associated with multiple neurodegenerative illnesses, including Parkinson’s disease. This protein is also a prominent component of Lewy bodies and Lewy neurites (abnormal protein clusters on the inside of neurons). Lewy bodies and Lewy neurites are pathological hallmarks of several neurological disorders collectively known as synucleinopathies. Synucleinopathies include Parkinson’s disease; dementia with Lewy bodies; multiple system atrophy; and certain other neurological disorders. In synucleinopathies, the α-synuclein protein is believed to misfold and aggregate to form the protein structures that are thought to contribute to the pathology of the disease.
Current treatment options for Parkinson’s disease and other synucleinopathies focus on providing symptomatic benefit; our goal is to slow the progression of disease. To achieve this, we have developed monoclonal antibodies intended to slow or reduce the neurodegeneration associated with α-synuclein misfolding and/or its transmission. The lead candidate in this portfolio, PRX002, is expected to begin Phase 1 testing in 2014.
Our scientists have maintained an interest in the biology of T-cell migration. In other words, determining how T-cells leave the circulatory system by attaching and migrating across blood vessel walls. We have made several fundamental scientific contributions that further our understanding of cell adhesion molecules and their role in allowing particularly pathogenic cells and proteins to transfer out of the circulatory system and into tissue sites where they initiate the damage associated with a variety of autoimmune diseases. These initial discoveries led to the development of Tysabri® (natalizumab), a highly effective drug that prevents inflammatory cells from entering the brain during periods of multiple sclerosis relapse, which is marketed by Biogen Idec.
There is a significant amount of literature suggesting Th17 cells are the primary cause of a variety of inflammatory diseases. Since Th17 cells represent a relatively small proportion of the overall T-cell population, we have focused on targeting these cells specifically in order to leave the majority of immune function intact.
Our approach is designed to prevent Th17 cells from leaving the blood vessels and infiltrating the tissue by blocking the interaction of a key cell adhesion protein, explicitly expressed on the surface of Th17 cells, with its binding partner on the blood vessel. As such, our approach differs with some other approaches that have focused directly on targeting individual cytokines released by Th17 cells, particularly IL-17. The same cell adhesion molecule is called the melanoma cell adhesion molecule (MCAM). MCAM appears to be critical for Th17 migration and has been reported to be upregulated on a variety of metastatic tumor cells that may utilize a similar molecular approach to spread to new tissue sites. We believe there is enormous potential in conducting discovery and development work in Th17-mediated inflammatory diseases and cancer. We are testing a portfolio of monoclonal antibodies that we have developed to selectively block MCAM-mediated cell adhesion. We have selected a lead candidate for clinical development and anticipate initiating Phase 1 clinical testing in 2015.
Our Discovery team continues to deliver new approaches to Prothena’s pipeline in a number of therapeutic areas as we progress our lead programs clinically. We are confident the important discoveries made to date and continued future innovation will ensure a profound impact on human health for decades to come.
Prothena Corporation is a clinical-stage biotechnology company with a portfolio of novel monoclonal antibodies that may offer new treatments for diseases associated with protein misfolding or cell adhesion.
Prothena’s research and development pipeline includes three lead therapeutic antibody programs that we are advancing aggressively: NEOD001 for the treatment of AL and AA Amyloidosis; PRX002 for the treatment of Parkinson’s disease; and PRX003 for the potential treatment of inflammatory disease and metastatic cancers. NEOD001 is in Phase 1 development, and in both 2014 and 2015, we anticipate moving one or more of our other product candidates into the clinic.
Prothena’s pipeline includes several discovery-stage programs studying antibodies that may offer potential treatments for Alzheimer’s disease and Type 2 Diabetes. The Company continues to generate additional novel antibodies against other targets involved in protein misfolding and cell adhesion.
Prothena employs three distinct strategies to ensure we are allocating our resources towards the appropriate antibody and target disease, potentially increasing the likelihood each compound will complete Phase 3 development successfully. We leverage our insight into the pathology of diseases involving protein misfolding and cell adhesion to employ biomarker endpoints in order to detect signals of clinical efficacy early in the clinical development process. We collaborate with scientists who are recognized as experts in our disease areas of interest to test and characterize our potential therapeutic antibody candidates. We seek feedback and guidance on our programs from leading clinical experts. We believe these strategies give us the opportunity to make the most educated decisions about our compounds throughout the development process.
Prothena Corporation has attracted an elite team with an extensive track record in discovering and developing therapeutics that have become the leading commercial products in their respective therapeutic categories. The team brings this heritage to Prothena with the vision of continuing to create and develop novel antibody-based therapies that benefit a diverse population of patients.