Benzinga | Nov 4, 2020 08:32AM EST

Prothena Announces Presentations On Two Programs From Its Alzheimer's Disease Portfolio At CTAD 2020

* Next generation anti-A? antibodies being developed for subcutaneous administration to improve access for patients with Alzheimer's disease

* Multi-immunogen A?-tau vaccine being developed for the prevention and treatment of Alzheimer's disease

DUBLIN, Ireland, Nov. 04, 2020 (GLOBE NEWSWIRE) -- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical company with expertise in protein dysregulation and a diverse pipeline of investigational therapeutics for neurodegenerative and rare peripheral amyloid diseases, today announced that it will present preclinical data from two programs in its Alzheimer's disease portfolio at the 13th Clinical Trials on Alzheimer's Disease Conference 2020 (CTAD 2020). Prothena's programs being highlighted at CTAD 2020 are next generation anti-A? antibodies for subcutaneous administration to improve patient access, and a multi-immunogen vaccine that targets key A? and tau epitopes, the two main pathological proteins involved in the cause and progression of Alzheimer's disease, for the prevention and treatment of Alzheimer's Disease. The two programs are part of Prothena's Alzheimer's disease portfolio that includes antibodies, vaccines and small molecules.

"After years of foundational research by our scientists and advances by others, we believe the field is on the precipice of being able to offer patients the first generation of drugs to slow the relentless progression of neurodegenerative diseases such as Alzheimer's," stated Wagner Zago, PhD, Chief Scientific Officer of Prothena. "Due to the high prevalence of Alzheimer's disease, these first-generation approaches will face significant challenges related to patient access due to high required dose levels, route of administration, manufacturing and distribution limitations. To address these limitations, Prothena has developed a portfolio of next generation therapies with a focus on delivering greater patient access through, for example, highly potent anti-A? antibodies that can be delivered through convenient subcutaneous administration. We have accomplished this by applying our knowledge around the structural binding characteristics of antibodies to design and screen novel immunotherapies with improved binding properties to key epitopes to produce the desired clinical effect."

Next generation anti-A? antibodies

Monoclonal antibodies targeting key epitopes within the N-terminus of A? have demonstrated that reducing amyloid plaque burden is associated with the slowing of clinical decline in Alzheimer's disease. To address the growing prevalence of Alzheimer's disease with a therapeutic that can be made widely accessible to patients, Prothena has developed highly potent anti-A? antibodies that retain or improve key attributes that are thought to underlie the observed efficacy of N-terminally directed therapeutics such as aducanumab, with the aim of offering similar or improved efficacy with convenient subcutaneous dosing regimens. Prothena antibodies demonstrated a higher binding strength to amyloid than aducanumab; specifically, antibodies with as much as an 11-fold greater affinity/avidity for fibrillar A? than aducanumab that also neutralized soluble, toxic (i.e., oligomeric) A? species. Prothena antibodies were also shown to recognize A? pathology to a greater extent than aducanumab, demonstrating more extensive plaque area binding at lower antibody concentrations, which are estimated to be clinically relevant exposures in the central nervous system following systemic dosing.

The poster can be found as follows:

* Title: Novel Amyloid Beta Monoclonal Antibodies with Superior Binding Properties: Potential for More Convenient Dosing and Greater Patient Access in Alzheimer's Disease

* Session: Abstract # P81, New therapies and clinical trials

* Presenter: Wagner Zago, PhD, Chief Scientific Officer

Multi-Immunogen A?-Tau Vaccine

Preclinical models suggest that A? and tau act synergistically in the development of Alzheimer's disease; however, the majority of vaccines and passive immunotherapies under development target only one of these two pathological features. Prothena is developing a multi-immunogen vaccine (MIV) that targets key epitopes wihin the A? and tau proteins. The MIV is a single vaccine and is being developed for the prevention and treatment of Alzheimer's disease. The A?-tau MIV generates polyclonal responses against key epitopes within the N-terminal of A? and a key region of tau to promote amyloid clearance and blockade of tau transmission. Immunohistochemistry using sera from immunized animals demonstrated an appropriate and balanced immune response with antibodies that react to both A? plaques and tau tangles at concentrations expected to be reached in CNS following immunization and resultant titer generation.

The poster can be found as follows:

* Title: Development of a Dual A?-Tau Vaccine for the Prevention and Treatment of Alzheimer's Disease

* Session: Abstract # P80, New therapies and clinical trials

* Presenter: R. Barbour, Senior Director Antibody and Assay Development