Prothena Down 40% Year to Date: What Lies Ahead for the Stock?

Shares of Prothena Corporation (PRTA) have plunged 40% year to date against the industry’s gain of 6.6% as pipeline setbacks continue to weigh on the stock.While the company is striving hard to advance its other pipeline projects following the discontinuation of birtamimab's development, the ride continues to be bumpy.Image Source: Zacks Investment ResearchPRTA’s Recent Updates on PRX012In late August, PRTA provided an update on pipeline candidate PRX012. The company also announced results from the phase I ASCENT program on PRX012 in participants with early symptomatic Alzheimer’s disease (AD).Results from this phase I program demonstrated PRX012 as a potential once-monthly, subcutaneous anti-amyloid beta (Aβ) antibody with stable pharmacokinetics, low anti-drug antibodies, low injection site reactions, and dose- and time-dependent reductions in amyloid plaque.At the 400 mg dose level, this AD candidate demonstrated a mean reduction in amyloid PET to 27.47 centiloids (CL) at month 12, while most FDA-approved anti-Aβ antibodies have defined amyloid negativity thresholds of ≤30 CL or ≤24.1 CL.However, PRX012 was associated with higher overall ARIA-E rates relative to FDA-approved anti-Aβ antibodies. This observation makes the candidate less appropriate for the patients studied in the ASCENT clinical program. When ARIA-E occurred, the characteristics were similar to those reported following treatment with other anti-Aβ antibodies.As previously communicated by the company, Prothena plans to explore potential partnership interest to advance PRX012 and its preclinical PRX012-TfR (transferrin receptor) antibody.Based on the profile observed in the ASCENT clinical program and the feasibility work completed on its preclinical Aβ–transferrin receptor antibody surrogate, management believes this approach could significantly reduce the risk of ARIA and rapidly clear amyloid plaque with a once-monthly subcutaneous administration.Preclinical data on the candidate have demonstrated substantially increased brain exposure and facilitated rapid targeting of Aβ plaques in an APP/PS1 transgenic mouse model.Updates on PRX004In early August, Prothena announced that partner Novo Nordisk (NVO) will advance coramitug, a potential first-in-class amyloid depleter antibody, into a phase III program for ATTR amyloidosis with cardiomyopathy (ATTR-CM) in 2025.Coramitug was initially developed by Prothena and was acquired by Novo Nordisk in July 2021.Per the terms of the deal with NVO, Prothena is eligible to receive up to $1.2 billion upon achievement of clinical development and sales milestones, including the $100 million earned to date. Prothena is eligible to earn a clinical milestone payment when prespecified enrollment criteria are met in the phase III study.Pipeline Setbacks Hurt PRTA StockIn May 2025, PRTA announced the discontinuation of the development of the pipeline candidate, birtamimab.The decision to discontinue comes after the late-stage AFFIRM-AL clinical study evaluating birtamimab in patients with AL amyloidosis did not meet its primary endpoint. Birtamimab was a wholly owned potential best-in-class anti-amyloid antibody for the treatment of AL amyloidosis.Thereafter, in June 2025, PRTA announced a 63% workforce reduction to streamline operating costs, ensuring continued support for its wholly owned programs, partnered program obligations, and planned business development initiatives.Partner Roche Will Advance Parkinson's Disease DrugIn June 2025, partner Roche (RHHBY) announced its decision to advance prasinezumab into phase III development for early-stage Parkinson's disease, with initiation expected by the end of 2025.The candidate is being evaluated in ongoing open label extensions (OLEs) of the phase II PASADENA and phase IIb PADOVA clinical trials. Both studies are being conducted by Roche.What’s Next for PRTA?RHHBY’s decision to advance the candidate despite mixed data bodes well for PRTA.Roche has the sole responsibility for developing and commercializing prasinezumab and will pay double-digit teen royalties on net sales of the candidate to Prothena.PRTA is also advancing an early-stage pipeline of programs for several potential neurological indications with Bristol Myers (BMY).BMS-986446 is a best-in-class anti-tau, MTBR-specific antibody that is being investigated for the potential treatment of AD.Bristol Myers is conducting the phase II TargetTau-1 clinical trial in approximately 310 patients with early AD, with primary completion expected in 2027.BMY is also conducting a phase I open-label single-dose clinical trial to assess a subcutaneous administration. Bristol Myers Squibb is responsible for all development, manufacturing, and commercialization.PRX019, a potential treatment for neurodegenerative diseases, is also being developed in collaboration with BMY.PRTA has initiated a phase I first-in-human clinical trial on PRX019 to evaluate the safety, tolerability, immunogenicity and pharmacokinetics of single ascending and multiple doses in healthy adults. The phase I study is expected to be completed in 2026.While the progress with partnered programs is encouraging, the setbacks with wholly owned programs are a major setback for PRTA.PRTA currently carries a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here. 7 Best Stocks for the Next 30 DaysJust released: Experts distill 7 elite stocks from the current list of 220 Zacks Rank #1 Strong Buys. They deem these tickers "Most Likely for Early Price Pops."Since 1988, the full list has beaten the market more than 2X over with an average gain of +23.5% per year. So be sure to give these hand picked 7 your immediate attention. See them now >>Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Roche Holding AG (RHHBY): Free Stock Analysis Report Bristol Myers Squibb Company (BMY): Free Stock Analysis Report Novo Nordisk A/S (NVO): Free Stock Analysis Report Prothena Corporation plc (PRTA): Free Stock Analysis ReportThis article originally published on Zacks Investment Research (zacks.com).Zacks Investment ResearchWeiter zum vollständigen Artikel bei Zacks Weiter zum vollständigen Artikel bei Zacks