Prothena Q4 2025 Earnings: Two Partnered Programs Enter Phase III, Cash Position Exceeds Guidance

Prothena Corporation reported fourth-quarter 2025 adjusted loss per share of 45 cents, in line with estimates. Revenues totaled $0.02 million, missing estimates of $3.0 million. The company ended 2025 with $308.4 million in cash, cash equivalents and restricted cash, topping its prior guidance of $298 million.

Roche advanced Parkinson's drug prasinezumab into the Phase III PARAISO trial, targeting about 900 participants with primary completion expected in 2029. Novo Nordisk pushed cardiomyopathy candidate coramitug into the Phase III CLEOPATTRA study with roughly 1,280 patients, also aiming for primary completion in 2029. Roche expects peak sales potential of greater than $3.5 billion (unadjusted) of prasinezumab.

In an exploratory prasinezumab subset of patients already on levodopa, Prothena reported a 40% relative reduction in motor progression on MDS‑UPDRS Part III with nominal statistical support. Coramitug's 60 mg/kg dose delivered a 48% reduction in NT‑proBNP versus placebo and echocardiographic signs of favorable cardiac remodeling, strengthening its Phase III rationale. The phase II data for coramitug supports the ongoing phase III CLEOPATTRA study.

While coramitug's biomarker performance was strong, the Phase II 6‑minute walk test showed only a numerical, non‑significant improvement at the 60 mg/kg dose. Novo Nordisk attributed the lack of statistical separation to the modest sample size of 105 patients and the relatively short 12‑month study duration.

Management underscored the economic leverage in its partnered portfolio, which could yield up to $105 million in clinical milestones in 2026 tied primarily to coramitug enrollment and a PRX019 decision from Bristol Myers Squibb. Prothena expects to earn a clinical milestone in the first half of 2026 if the prespecified enrollment criteria are met in the ongoing phase III study by Novo Nordisk. Across all alliances, the company highlighted roughly $3.0 billion in potential future milestone payments on top of prospective royalties. The candidate could earn Prothena up to $1.23 billion in development and sales milestones, including $100 million already received, with additional payments tied to phase III enrollment targets.

Bristol Myers Squibb fully enrolled its Phase II TargetTau‑1 trial in about 310 patients, with primary completion targeted for the first half of 2027 and Fast Track status already secured. BMS-986446 (formerly PRX005) is a best-in-class anti-tau, MTBR-specific antibody for the potential treatment of Alzheimer's Disease. Bristol Myers Squibb also conducted a phase I open-label single-dose clinical study to assess subcutaneous administration. Prothena expects to earn a milestone payment by the end of 2026 if Bristol Myers decides to further develop PRX019.

Interim Phase I ASCENT results for PRX012 showed mean amyloid PET levels falling to roughly 27.5 centiloids at 12 months on monthly 400 mg subcutaneous dosing. Preliminary 18‑month data suggested further reduction to about 16 centiloids, with 75% of patients achieving amyloid negativity by the study's predefined threshold. Despite encouraging efficacy, PRX012's ARIA‑E rates in ASCENT were described as noncompetitive versus approved anti‑amyloid antibodies, raising commercial and regulatory questions. In response, Prothena is pivoting toward a transferrin receptor‑enabled PRX012 program aimed at reducing ARIA risk while preserving or enhancing brain exposure.

The company unveiled its CYTOPE technology and early TDP‑43 data in aggressive ALS mouse models, demonstrating systemic central nervous system activity and reduced brain and muscle pathology. Importantly, Prothena reported attenuation of RNA mis‑splicing, supporting CYTOPE's ability to drug historically hard‑to‑reach intracellular targets. Prothena also cited an ongoing CYTOPE research collaboration with a major pharma player and approval of a 2026 share redemption program.

Net cash used in operating and investing activities was $163.7 million, better than expected, while the full‑year net loss of $244.1 million landed squarely within the guided range. For full-year 2025, the company reported total revenues of $9.7 million, which declined 93% year over year. For full-year 2025, the company recorded a net loss of $3.97 per share, wider than a loss of $2.27 per share in 2024.

Research and development expenses plunged 71% year over year to $14.6 million, driven by reduced clinical trial, manufacturing, personnel and consulting costs. General and administrative expenses were $12.6 million, down 25% year over year. As of Dec. 31, 2025, Prothena had $308.4 million in cash, cash equivalents and restricted cash, compared with $331.7 million as of Sept. 30, 2025. It had no debt.

The company expects 2026 net cash burn from operating and investing activities to be in the range of $50 million-$55 million. It expects the year-end cash, cash equivalents and restricted cash midpoint to be approximately $255 million. Net loss for 2026 is projected to be in the $67 million to $72 million range.