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]