PRTA - Prothena Biosciences' Unique Approach To Protein Misfolding Could Be The Future

2023-05-07 02:28:01 ET

Summary

• Prothena's recent collaboration with Walgreens is expected to drive recruitment for Prothena's ongoing ASCENT-2 safety and tolerability trial of PRX012.
• PRX012, an anti-amyloid beta antibody, has shown superior binding and clearance of toxic A? species compared to other approved and investigational molecules in preclinical studies.
• Prothena's other investigational therapeutics, including Prasinezumab, Birtamimab, and PRX004, have also demonstrated positive results in preclinical and clinical studies, offering hope for patients and caregivers facing devastating diseases.

Prothena Biosciences ( PRTA ) has made significant strides in the field of protein dysregulation, with a pipeline of investigational therapeutics that show great promise in treating devastating diseases such as Alzheimer's and Parkinson's. The company's four lead programs—PRX012, Prasinezumab, Birtamimab, and PRX004—all target different proteins associated with these diseases, using innovative approaches that have shown positive results in preclinical and clinical studies.

Prothena's products appear to be superior to their competitors due to their high binding affinity and ability to target multiple aggregated forms of proteins, which could prevent further disease progression and potentially halt organ deterioration. Additionally, the company's partnerships with leading pharmaceutical companies like Roche demonstrate their strong position in the industry and their ability to leverage the expertise of others in the field.

From a financial standpoint, Prothena's balance sheet appears stable and their recent results have been encouraging, with positive clinical data for their lead programs and a growing pipeline of other investigational therapeutics . With a strong scientific foundation and a clear focus on unmet medical needs, Prothena appears to be well-positioned for future success in the biotech industry. Investors should consider Prothena as a potential investment opportunity with significant upside potential.

Financials

Recently, Prothena Biosciences released its financial results for the fourth quarter and full year of 2022. In Q4, a net profit of $6.3 million was recorded. However, there was an overall annual deficit of $116.9 million due to R&D expenses incurred. Total revenue earned in the 4th quarter was reported as $49.9 million while throughout the entire fiscal year it was $53.9 million - a substantial improvement compared to the figures from the previous year which were $1.2 million and $200.6 million, respectively. The surge in sales can be attributed to a milestone payment receipt from Novo Nordisk (NYSE: NVO ) totaling $40.0 million plus additional income accrued from the Bristol Myers Squibb (NYSE: BMY ) partnership amounting to $9.9 million in Q4 and $13.9 million over the whole year.

Research and development expenses were listed as $36.9 million and $135.6 million during the same timeframe being analyzed, higher than the former yearly costs of $22.1 million and $82.3 million, respectively. Steeper personnel, clinical trial, and manufacturing fees contributed to this surge, but some of these costs were ultimately balanced by reduced expenditure associated with Roche's NNC6019 . Separately, general and administrative expenses for this period hit counts of $13.1 million and $49.9 million in Q4 and 2020, respectively; increased staffing and consulting costs were partly offset by decreased legal outlays, while non-cash, share-based compensation expenses also exceeded earlier numbers at $7.4 million for Q4 and $31.3 million for 2020.

Despite recording an overall loss in 2022, Prothena still maintains sound finances with no debt and $712.6 million in reserves as of December 31st. Talking about 2023, they predict using between $213 to $229 million on operating or investing activities, leading to a forecasted net loss of $250 to $275 million inclusive of $46 million in non-cash, share-oriented expense. This should leave them with roughly $512 million remaining by the end of the year.

Pipeline

Prothena Biosciences has created a range of potential therapeutics to address protein problems in diseases like Alzheimer's and Parkinson's. PRX012 is an anti-amyloid beta (A?) antibody which targets many different forms of A?, binding tightly to stop it forming and growing further and causing the body's immune system to clear out the A? connected with Alzheimer's disease. Prasinezumab is a monoclonal antibody that aims at alpha-synuclein (?-syn) build up in Parkinson's and related conditions, reducing its impact on the brain and protecting neurons from harm. Birtamimab is another monoclonal antibody treatment targeting amyloid fibrils associated with AL amyloidosis. This therapy lets the body’s own defenses destroy the fibrils and could help avoid organ failure. Finally, PRX004 is a monoclonal antibody using a misfolded form of transthyretin (TTR) to tackle (ATTR) amyloidosis, blocking them from joining together and sticking in place while also stimulating their clearance. These treatments have shown promising outcomes in both preclinical and clinical trials, bringing hope to patients and their carers when faced with these difficult cases.

Preliminary Findings Support PRX012 for Alzheimer’s Disease

Prothena Biosciences, an advanced clinical-stage biotech firm, has revealed new preclinical findings from its PRX012 program, a prospective anti-amyloid beta (A?) therapy candidate for Alzheimer's disease treatment. The outcomes of two preclinical trials were shared at the 2023 International Conference on Alzheimer's and Parkinson's Diseases. These studies contrast PRX012 with approved and experimental molecules, demonstrating PRX012's potential as a top-tier anti-A? treatment for Alzheimer's disease. PRX012 exhibited roughly 20 times greater affinity for A? protofibrils compared to lecanemab under identical conditions. Additionally, PRX012 elicited a more potent and substantial clearance of pyroglutamate-modified A? at lower concentrations than donanemab . This information contributes to the expanding evidence supporting PRX012's profile, which aims to target all aggregated A? forms with high binding potency.

PRX012 is presently undergoing Phase 1 clinical trials for Alzheimer's disease treatment. The preclinical findings show PRX012's high-affinity binding to beta-amyloid plaques and oligomers, leading to effective A? plaque occupancy and elimination at relatively lower antibody concentrations, potentially allowing for reduced administration volumes via subcutaneous delivery. PRX012's potential as a next-generation Alzheimer's disease therapy offering more convenient administration for patients and caregivers is substantial, especially considering the over 55 million people globally estimated to be living with Alzheimer's disease or other dementias. Prothena is dedicated to providing a patient-focused, best-in-class A?-targeting antibody capable of powerfully and safely depleting A? plaques.

Prothena Collaborates With Walgreens for ASCENT-2 Study

Prothena Biosciences has revealed a partnership with Walgreens to expedite the identification and enrollment of patients in Prothena's current ASCENT-2 clinical study, which assesses the safety and tolerability of PRX012. This potential top-tier anti-amyloid beta antibody is being developed for Alzheimer's disease treatment. Through this collaboration, Walgreens will employ its nationwide reach, array of healthcare businesses, and regulatory framework to connect patient populations with Prothena's PRX012 clinical trial, which has received Fast Track status from the US Food and Drug Administration. Prothena asserts that Walgreens' distinct capabilities will enable the company to utilize them in engaging a wider and more diverse patient group for potential ASCENT-2 enrollment, thus hastening the development of the PRX012 program. The partnership also aims to address the historical exclusion of Black and Hispanic older adults from Alzheimer's disease clinical trials.

Walgreens' nearly 9,000 pharmacy locations and patient-approved clinical data will aid in identifying and interacting with potentially eligible patients and their caregivers in a convenient manner, informing them about Prothena's ASCENT-2 clinical study. Prothena's Phase 1 PRX012 single ascending dose and multiple ascending dose trials are in progress, with top-line results anticipated by the end of 2023.

Possible Mechanism Risks

Prothena Biosciences’ products have shown potential benefits for the treatment of various diseases. However, there are also potential risks associated with their mechanisms of action. PRX012 targets aggregated forms of A?, which are implicated in Alzheimer’s disease. However, A? is also a normal component of the brain, and has some physiological roles. Therefore, PRX012 may also bind to and interfere with the normal functions of A?, and cause adverse effects on the brain. Prasinezumab targets aggregated forms of alpha-synuclein (?-syn), which are involved in Parkinson’s disease and other synucleinopathies. However, ?-syn is also a normal protein that is expressed in various tissues, especially in the nervous system, and has some functions. Therefore, prasinezumab may also bind to and disrupt the normal functions of ?-syn, and cause adverse effects on the nervous system.

Birtamimab targets a conformational epitope on amyloid fibrils composed of immunoglobulin light chains ((LC)) in AL amyloidosis. However, LCs are also normal components of immunoglobulins, which are essential for the immune system and defense against infections. Therefore, birtamimab may also bind to and interfere with the normal functions of LCs or immunoglobulins, and cause adverse effects on the immune system. PRX004 targets a conformational epitope on misfolded forms of TTR in ATTR amyloidosis. However, TTR is also a normal protein that is synthesized in the liver and circulates in the blood plasma, where it binds to and transports thyroid hormones and retinol. Therefore, PRX004 may also bind to and disrupt the normal functions of TTR or its ligands, and cause adverse effects on the endocrine system or vision. Additionally, all of these products may induce an inflammatory response in the organs by activating immune cells, which could worsen the disease conditions.

Advantages Over Competitors

Prothena Biosciences' pipeline of investigational therapeutics for Alzheimer's and Parkinson's diseases have potential advantages over current competitors. In the Alzheimer's disease space, PRX012 stands out due to its high binding affinity for multiple aggregated forms of A?, including protofibrils and plaques , which are believed to be neurotoxic and responsible for cognitive decline and memory loss. This best-in-class anti-A? antibody may prevent further formation and growth of A? pathology, while triggering immune cell clearance, providing a more comprehensive approach than other monoclonal antibodies, such as aducanumab , that only target amyloid plaques.

Prasinezumab offers a unique approach in Parkinson's disease by targeting ?-syn aggregation, a key pathogenic feature of the disease. Unlike current therapies, such as levodopa , which only alleviate symptoms, prasinezumab may slow down or reverse the disease progression by blocking the spread of ?-syn pathology in the brain, protecting neurons from inflammation and degeneration. This mechanism of action is superior to other monoclonal antibodies, such as BIIB054, that only target aggregated forms of ?-syn or vaccines, such as AFFITOPE PD01A, that induce a humoral immune response.

Birtamimab shows promise in the treatment of AL amyloidosis, a rare systemic disorder caused by an abnormality of plasma cells in the bone marrow. By targeting a conformational epitope present on amyloid fibrils composed of immunoglobulin LCs, birtamimab may promote clearance of amyloid deposits in vital organs, potentially halting organ deterioration. This mechanism of action is superior to other monoclonal antibodies, such as daratumumab or isatuximab , that target CD38 or CD38-expressing plasma cells, respectively, but do not directly affect amyloid deposition.

PRX004 targets misfolded forms of TTR, a protein that forms amyloid deposits in the peripheral nerves and heart in patients with hereditary and wild-type ATTR amyloidosis. By depleting the misfolded TTR species that are associated with toxicity and disease progression, while preserving the normal tetrameric form of the protein that has essential physiological functions, PRX004 may halt or reverse the disease progression. This mechanism of action is superior to other monoclonal antibodies, such as inotersen or patisiran , that target TTR mRNA or RNA interference, respectively, but do not directly affect misfolded TTR species.

Conclusion

Prothena Biosciences is a biotechnology company that appears to be set for long-term growth within the neurodegenerative disease space. By developing investigational therapeutics targeting protein dysregulation in debilitating diseases such as Alzheimer’s and Parkinson's, the company has generated encouraging results from preclinical and clinical trials, offering hope to those suffering with these conditions and their carers. Furthermore, established collaborations between Prothena and firms like Roche and Walgreens illustrate the company's capacity to form strategic partnerships designed to foster further advancement of its therapies and expand patient access. While it may not currently have profitable financials, the overall trend in biotech remains progressive, with increased investment and heightened demand for innovative treatments. Boasting strong scientific knowledge, a pioneering approach, and meaningful alliances, Prothena Biosciences stands ready to make a tangible contribution to the arena of neurodegenerative diseases and reward long-term investors with mutual benefits.

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