Core Viewpoint - Prothena Corporation (PRTA) has experienced a significant decline in share price, dropping 36.8% over the past year, primarily due to setbacks in its pipeline, particularly the failure of its candidate birtamimab in a late-stage study [1][6]. Financial Performance - The company has reported inconsistent earnings over the last four quarters, with losses widening due to increased research and development expenses and the impact of pipeline setbacks, including the discontinuation of birtamimab [2]. - Prothena's earnings have missed estimates in each of the last four quarters, with an average negative surprise of 26.72% [2]. Pipeline Setbacks - In May 2025, Prothena announced the discontinuation of birtamimab after the AFFIRM-AL study failed to meet its primary endpoint, removing a near-term value driver [3]. - The termination of birtamimab has significantly reduced near-term catalysts for the stock and shifted the company's strategic focus toward earlier-stage assets like PRX012, which are several years away from potential commercialization [4]. Workforce and Cost Management - In June, Prothena announced a 63% workforce reduction to streamline operating costs while ensuring continued support for its wholly owned programs and partnered program obligations [7]. Partnered Programs Progress - Prothena's pipeline progress is largely driven by partnered assets rather than wholly owned programs [8]. - Partner Novo Nordisk is evaluating coramitug in the phase III CLEOPATTRA program for ATTR cardiomyopathy, which could earn Prothena up to $1.23 billion in development and sales milestones [9]. - Roche has initiated the phase III PARAISO study on prasinezumab for early-stage Parkinson's disease, indicating ongoing commitment to this collaboration [10]. Collaboration Agreements - Prothena has a worldwide collaboration agreement with Roche, having received $135 million to date, with potential for up to $620 million in additional milestone payments and royalties on future sales [11]. - Bristol Myers Squibb is conducting a phase II study for its anti-tau antibody BMS-986446 in Alzheimer's disease, with primary completion expected in 2027 [12]. Ongoing Development - Prothena has initiated an early-stage first-in-human study on PRX019, with completion expected in 2026 [14].

Core Insights - Prothena Corporation's shares have decreased by 40% year-to-date, contrasting with a 6.6% gain in the industry, primarily due to pipeline setbacks [1][8] - The company is working to advance other pipeline projects after halting the development of birtamimab, but challenges persist [1] Pipeline Updates - Prothena provided an update on PRX012, a candidate for early symptomatic Alzheimer's disease, showing promising results in a phase I program [3][4] - PRX012 demonstrated a mean reduction in amyloid PET to 27.47 centiloids at the 400 mg dose level after 12 months, which is favorable compared to FDA-approved anti-Aβ antibodies [4] - However, PRX012 exhibited higher overall ARIA-E rates, raising concerns about its suitability for the studied patient population [5] - The company plans to seek partnerships to advance PRX012 and its preclinical PRX012-TfR antibody, which may reduce ARIA risks and enhance amyloid clearance [6][8] Recent Developments - Novo Nordisk will advance coramitug, an amyloid depleter antibody, into a phase III program for ATTR amyloidosis with cardiomyopathy in 2025, which Prothena initially developed [9] - Prothena is eligible for up to $1.2 billion in milestone payments from Novo Nordisk, having already earned $100 million [10] Setbacks and Workforce Changes - The discontinuation of birtamimab's development was announced in May 2025 after it failed to meet primary endpoints in a late-stage study [11] - Following this, Prothena implemented a 63% workforce reduction to streamline costs and support ongoing programs [12] Partnered Programs - Roche is advancing prasinezumab into phase III development for early-stage Parkinson's disease, with initiation expected by the end of 2025 [13][14] - Prothena will receive double-digit teen royalties on net sales of prasinezumab [14] - Bristol Myers is conducting phase II and phase I trials for potential Alzheimer's treatments, with Prothena collaborating on several early-stage programs [15][16] Overall Outlook - Despite progress in partnered programs, setbacks in wholly owned programs present significant challenges for Prothena [17]

Core Insights - AstraZeneca (AZN) reported disappointing results from two late-stage studies evaluating its investigational antibody anselamimab for treating light chain (AL) amyloidosis [1][7] - Both studies aimed to assess the efficacy of anselamimab plus standard care against placebo, focusing on all-cause mortality and cardiovascular hospitalizations [2][3] - The treatment did not achieve statistical significance for the primary endpoint in either study, although a clinically meaningful improvement was noted in a prespecified subgroup [3][7] - AstraZeneca plans to conduct a full analysis of the results and present findings at a future medical meeting [3][7] Disease Context - AL amyloidosis is caused by amyloid protein deposits due to defective plasma cells, leading to organ damage and potential premature death, primarily from cardiac failure [4] - Approximately 74,000 people globally are affected by AL amyloidosis [4] Market Performance - Year to date, AstraZeneca's shares have increased by 7%, contrasting with a 1% decline in the industry [5] Industry Setbacks - AstraZeneca is not alone in facing setbacks in the AL amyloidosis treatment space, as Prothena (PRTA) also reported a failure with its drug birtamimab in a similar study [8][9] - Prothena's AFFIRM-AL study did not meet its primary endpoint, leading to the termination of birtamimab's development and a significant workforce reduction [9]