Prothena Stock

Prothena Corporation plc operates as a late-stage clinical biotechnology company.

The company has expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to change the course of devastating rare neurodegenerative and peripheral amyloid diseases.

The company is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. The company’s wholly-owned programs include birtamimab for the potential treatment of AL amyloidosis and a portfolio of programs for the potential treatment of Alzheimer’s disease, including PRX012, which targets Amyloid beta (Aß), and PRX123, a novel dual Aß-tau vaccine. The company’s partnered programs include prasinezumab, in collaboration with Roche for the potential treatment of Parkinson’s disease and other related synucleinopathies, and programs that target tau (PRX005), TDP-43, and an undisclosed target (PRX019) in collaboration with Bristol Myers Squibb (BMS) for the potential treatment of Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases.

Strategy

The company’s pipeline reflects its deep understanding of the contribution of these toxic proteins to the cause and progression of disease. The company leverages pioneering protein dysregulation science to develop novel therapeutic solutions that directly target pathogenic proteins in order to change the course of devastating neurodegenerative and rare peripheral amyloid diseases. The company is advancing a broad pipeline of therapies with novel mechanisms of action that are uniquely suited to address unmet medical needs in targeted patient populations.

The company plan is to become a fully integrated research, development, and commercial biotechnology company. Three late-stage programs in the company’s pipeline are ongoing, including AFFIRM-AL, a registration-enabling Phase 3 study of birtamimab in Mayo Stage IV patients with AL amyloidosis being conducted under a Special Protocol Assessment (SPA) agreement with FDA with significance level of p = 0.10, a Phase 2b PADOVA study of prasinezumab in patients with early Parkinson’s disease being conducted by Roche, and a Phase 2 study of NNC6019 (formerly PRX004) in patients with ATTR cardiomyopathy being conducted by Novo Nordisk. In addition, the company is advancing a robust portfolio of Alzheimer’s disease programs designed to target the underlying disease pathology. These programs include PRX012, an anti-Aß antibody designed to be best-in-class and dosed subcutaneously; PRX005, an investigational antibody that specifically targets a key epitope within the microtubule binding region (MTBR) of tau, and a potential best-in-class treatment, which is partnered with BMS; and PRX123, a dual Aß-tau vaccine for the treatment and prevention of Alzheimer’s disease.

The key elements of the company’s strategy are to concentrate its discovery and development efforts in areas where it has decades of scientific expertise and experience; focus on diseases that lack effective therapies; and pursue strategic business development opportunities and collaborations and leverage external resources.

Research and Development Pipeline

The company’s clinical research and development pipeline includes five therapeutic antibody programs in clinical development: birtamimab for the potential treatment of AL amyloidosis; prasinezumab, in collaboration with Roche, for the potential treatment of Parkinson’s disease and other related synucleinopathies; NNC6019, which is being developed by Novo Nordisk, for the potential treatment of ATTR amyloidosis; PRX012 for the potential treatment of Alzheimer’s disease; and PRX005, in collaboration with BMS, for the potential treatment of Alzheimer’s disease. AL amyloidosis and ATTR amyloidosis are diseases caused by misfolded, pathogenic forms of light chain (AL) or transthyretin (ATTR) protein that deposit as amyloid in vital organs, such as the heart.

In addition to its clinical development pipeline, the company has a number of discovery- and late-preclinical-stage programs targeting proteins implicated in neurological diseases including Aß and tau for the potential treatment and prevention of Alzheimer’s disease and other neurodegenerative disorders, and TDP-43 for the potential treatment of amyotrophic lateral sclerosis. TDP-43 and a third undisclosed neurodegenerative target are the focus of the company’s collaboration with BMS. The company has also prioritized and selected the lead candidate for its Alzheimer’s disease vaccine program, PRX123.

The company has deep expertise in antibody targeting and have developed a diverse pipeline that includes antibody, as well as small molecule and vaccine approaches. The company has a diverse portfolio positions it to make an impact on a broad spectrum of diseases and it may also pursue opportunities in other modalities, such as gene and cell therapies.

In October 2020, the company announced that Roche and Prothena will advance prasinezumab into a late-stage Phase 2b study in patients with early Parkinson’s disease.

In December 2013, the company entered into the License Agreement with Roche to develop and commercialize certain antibodies that target a-synuclein, including prasinezumab, which are referred to in this report collectively as Licensed Products. In May 2021, the company announced that the first patient had been enrolled in PADOVA, a global Phase 2b study of prasinezumab in patients with early Parkinson’s disease.

NNC6019 is an investigational antibody designed to deplete amyloid associated with disease pathology in hereditary and wild type ATTR amyloidosis, without affecting the native, normal tetrameric form of the protein. The company completed a Phase 1 study with NNC6019 in patients with hereditary forms of ATTR amyloidosis, in which NNC6019 was demonstrated to be safe and well tolerated.

On July 12, 2021, the company announced that it and Novo Nordisk entered into a definitive purchase agreement under which Novo Nordisk acquired its clinical stage antibody NNC6019 and broader ATTR amyloidosis business.

PRX005 is designed to be a best-in-class anti-tau antibody that specifically binds with high affinity the R1, R2, and R3 repeats within the microtubule binding region (MTBR) of tau and targets both 3R and 4R tau isoforms. In June 2021, the company announced that BMS exercised its option under the global neuroscience research and development collaboration to enter into an exclusive U.S. license for PRX005.

In March 2018, the company entered into the Master Collaboration Agreement (the Collaboration Agreement) with Celgene (which was acquired by BMS in November 2019), under which Celgene (BMS) may elect in its sole discretion to exclusively license rights to develop and commercialize antibodies targeting tau, TDP-43 and an undisclosed target.

In June 2021, the company announced that BMS exercised its option under the global neuroscience research and development collaboration to enter into an exclusive U.S. license for PRX005.

PRX012 is an investigational antibody that targets Aß, or Amyloid Beta, a protein implicated in Alzheimer’s disease. The company’s scientists have advanced the understanding of the biology of Alzheimer’s disease and made particularly impactful and fundamental discoveries that elucidated the role amyloid plays in the disease.’

The company is advancing its lead candidate, PRX012, as a next-generation approach for subcutaneous administration to improve access for patients with Alzheimer’s disease. In March 2022, the company announced the FDA clearance of the IND for PRX012 and the initiation of a Phase 1 single ascending dose study to investigate the safety, tolerability, immunogenicity, and pharmacokinetics of PRX012 in both healthy volunteers and patients with Alzheimer’s disease. In April 2022, the company announced that the FDA granted Fast Track designation for PRX012 for the treatment of Alzheimer’s disease. The FDA’s Fast Track designation program is designed to expedite the development and review of drugs intended to treat a serious condition, such as Alzheimer’s disease, with evidence demonstrating the potential to address an unmet medical need. A multiple ascending dose portion of the Phase 1 study is ongoing. Topline data from the Phase 1 study is expected in 2023.

The company is also advancing several discovery and preclinical-stage programs for neurological diseases with significant unmet medical needs, such as Alzheimer's disease and amyotrophic lateral sclerosis (ALS). The company’s discovery and pre-clinical pipeline includes its proprietary dual Aß-tau vaccine program, as well as two programs (TDP-43 and an undisclosed target (PRX019)) that are the focus of its collaboration with BMS.

The company is developing a dual vaccine, PRX123, which concomitantly targets key epitopes within both the Aß and tau proteins. Preclinical models suggest that Aß and tau act synergistically in the development of Alzheimer’s disease; however, the majority of vaccines and passive immunotherapies under development today target only one of these two pathological features.

PRX123 is being developed for the potential prevention and treatment of Alzheimer’s disease. In preclinical studies, PRX123 has generated polyclonal responses against key epitopes within the N-terminal of Aß 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 Aß plaques and tau tangles at concentrations expected to be reached in CNS following immunization and resultant titer generation.

In March 2022, the company delivered an oral presentation at AD/PD 2022 on preclinical data demonstrating that PRX123 generated anti-Aß and anti-tau antibodies to enable phagocytosis of Aß and to neutralize tau. The company expects to file an investigational new drug application (IND) for PRX123 with the FDA in 2023.

Regulation

Any products manufactured or distributed by the company or on its behalf pursuant to FDA approvals are subject to continuing regulation by the FDA, including requirements for record-keeping, reporting of adverse events, and submitting product deviation reports to notify the FDA of unanticipated changes in distributed products. The packaging and labeling of all products developed by the company are also subject to FDA approval and ongoing regulation and oversight.

Intellectual Property

The company owns or holds exclusive licenses to a number of issued patents and pending patent applications in the U.S. and other jurisdictions, including Patent Cooperation Treaty applications. As of December 31, 2022, the company’s patent portfolio included the following families of patents or patent applications that it owns or has exclusively licensed from other parties:

Approximately 8 patent families related to AL or AA amyloidosis, including its birtamimab program, including a composition of matter patent anticipated to expire 2029 (subject to potential adjustments in patent term);

Approximately 16 patent families related to Parkinson’s disease and other synucleinopathies, including its prasinezumab program, including a composition of matter patent anticipated to expire in 2032 (subject to potential adjustments in patent term);

Approximately 10 patent families related to passive immunotherapy for Alzheimer's disease, including the company’s PRX005 and PRX012 programs; and

Approximately 17 patent families related to other potential targets of intervention and diseases, including PRX019, and other product candidates including vaccines.

University of Tennessee License Agreement

Under a License Agreement with the University of Tennessee Research Foundation, the company has exclusively licensed from the University of Tennessee its joint ownership interest in certain patents jointly owned with it. Those patents relate to the company’s program targeting amyloidosis (birtamimab).

Under a License Agreement with The Regents of the University of California, the company has exclusively licensed from the University of California its joint ownership interest in certain patents jointly owned with it. Those patents relate to the company’s program targeting Parkinson’s disease and other synucleinopathies (prasinezumab).

Elan License Agreement: Under an Amended and Restated Intellectual Property License and Contribution Agreement with Elan and certain of its affiliates, the company has exclusively licensed from Elan and those affiliates certain patents and patent applications owned by them, and exclusively sublicensed from Elan and those affiliates certain patents and patent applications owned by Janssen Alzheimer Immunotherapy. Subsequent to entering into this Agreement, Elan was acquired by Perrigo Company plc.

Manufacturing

Prasinezumab - Boehringer Ingelheim Biopharmaceuticals GmbH (BI) manufactured clinical supplies of the company’s drug candidate prasinezumab for its completed Phase 1a single ascending dose and Phase 1b multiple ascending dose clinical trials. Roche, with whom the company is collaborating on development of prasinezumab, is manufacturing clinical supplies for the ongoing Phase 2 and any subsequent clinical trials for prasinezumab. The company is dependent on Roche to manufacture these clinical supplies.

NNC6019 - Rentschler Biopharma SE (Rentschler) manufactured clinical supplies of the company’s drug candidate NNC6019 for its completed Phase 1 clinical trial. The company is dependent on Novo Nordisk, and its third party manufacturers if applicable, to manufacture clinical supplies of NNC6019.

Birtamimab - BI manufactured clinical supplies of the company’s drug candidate birtamimab for its prior Phase 1, Phase 2 (PRONTO) and Phase 3 (VITAL) clinical trials. Rentschler is the company’s third-party manufacturer of drug substance for its Phase 3 (AFFIRM-AL) clinical trial. Such drug substance manufactured by Rentschler has been demonstrated to be comparable to the drug substance manufactured by BI. Catalent Pharma Solutions, LLC (Catalent) is its third-party manufacturer of drug product for its Phase 3 (AFFIRM-AL) clinical trial, and this drug product has been demonstrated to be comparable to the drug product produced by BI. The company is dependent on Rentschler and Catalent to manufacture clinical supplies for its Phase 3 (AFFIRM-AL) clinical trial.

PRX005 - Catalent is the company’s third-party manufacturer of drug substance and Berkshire Sterile Manufacturing, LLC (Berkshire) is its third-party manufacturer for drug product. The company is dependent on Catalent and Berkshire to manufacture clinical supplies for its Phase 1 clinical trial and any subsequent clinical trials for PRX005.

PRX012 - Catalent is the company’s third-party manufacturer of drug substance and Berkshire is its third-party manufacturer for drug product. The company is dependent on Catalent and Berkshire to manufacture clinical supplies for its planned Phase 1 clinical trial and any subsequent clinical trials for PRX012.

Research and Development

The company’s research and development expenses totaled $135.6 million in 2022.

History

Prothena Corporation plc was founded in 2012.