Prothena (NASDAQ:PRTA) used its fourth-quarter and full-year 2025 results call to highlight partner-driven clinical momentum, updates from its wholly owned preclinical portfolio, and a sharper cash burn outlook for 2026. Management repeatedly emphasized that Prothena’s pipeline is primarily advanced through collaborations and that the company is focused on “captur[ing] the value embedded in our clinical partnerships,” while continuing to build optionality through platform and preclinical work.
Partner programs advance into late-stage trials
President and CEO Gene Kinney said 2025 brought “significant progress” in the company’s clinical pipeline, calling out two partner programs that moved into phase 3.
Swanson said Roche’s phase 3 decision was informed by results from two phase 2 trials, PADOVA and PASADENA, and open-label extension data. He highlighted an exploratory endpoint from PADOVA presented by Roche at ADPD 2025: in a subset of participants (about 75% of the PADOVA population) who were on stable levodopa, prasinezumab showed a 40% relative reduction in progression on MDS-UPDRS part 3 versus placebo at 24 months, with a nominal p-value of 0.0177. He said aspects of the phase 3 design were optimized, including requiring stable levodopa for all participants and extending minimum trial duration to 24 months.
Separately, Novo Nordisk advanced coramitug into the phase 3 CLEOPATTRA trial in ATTR cardiomyopathy (ATTR-CM), intended to enroll approximately 1,280 patients with primary completion expected in 2029. Swanson described coramitug as a potential first-in-class amyloid depleter antibody thought to deplete both deposited amyloid and circulating non-native transthyretin to prevent further deposition and improve organ function, including for patients on stabilizers or silencers.
In the phase 2 coramitug trial (12 months; 105 patients), Swanson said the 60 mg/kg dose produced a statistically significant reduction in NT-proBNP versus placebo, with a 48% difference and p=0.0017. He noted the six-minute walk test results showed a numerical improvement that was not statistically significant, attributing that to sample size and duration, and added that echocardiogram measures were broadly consistent with improvement compared with placebo. Swanson also said more than 80% of patients in both arms were receiving concomitant TTR stabilizers.
Bristol Myers Squibb programs: enrollment milestone and upcoming readout
Management also reviewed partnered programs with Bristol Myers Squibb (BMS). Swanson said BMS-986446, an anti-tau antibody designed to target a microtubule binding region (MTBR) epitope, achieved several 2025 milestones: completion of enrollment in the phase 2 TargetTau-1 trial (about 310 patients with early Alzheimer’s disease), completion of a phase 1 study evaluating a subcutaneous formulation, and receipt of Fast Track designation from the U.S. FDA for Alzheimer’s disease.
The TargetTau-1 study’s primary endpoint is change from baseline in brain tau deposition measured by tau PET at 76 weeks, with secondary endpoints including CDR sum of boxes and IDRSS. Prothena said it expects study completion in the first half of 2027.
Prothena is also conducting a phase 1 trial for PRX019 under its BMS agreement. Kinney said the phase 1 trial is on track for completion in 2026. In the Q&A, Kinney said Prothena will share the phase 1 results with BMS, but that “it will be up to them to decide what and how much of that information to share publicly.” CFO and Chief Strategy Officer Tran Nguyen added that BMS has global rights to PRX019, exercised those rights, and paid Prothena $80 million for the program.
Wholly owned pipeline: CYTOPE platform and PRX012-TfR direction
Vice President and Head of Discovery Research Phil Dolan introduced additional detail on Prothena’s CYTOPE technology, which he described as an intracellular targeting approach intended to reach “virtually any cell type” and enable precise targeting of intracellular disease pathways in brain and periphery through endosomal uptake and escape while preserving membrane and vesicle integrity after systemic administration.
The first disclosed CYTOPE program is an anti-phosphorylated TDP-43 CYTOPE for ALS. Dolan said it was designed to bind and degrade intracellular phosphorylated TDP-43 aggregates while preserving normal TDP-43 function. He pointed to preclinical data presented at the Society for Neuroscience congress showing systemic administration reduced brain and muscle pathology in an aggressive ALS mouse model and attenuated RNA missplicing in human neuronal cells and mice.
In a later Q&A exchange, Kinney said the platform appears to show “robust CNS activity” following systemic administration and that Prothena had not seen evidence of endosomal disruption that has challenged other approaches. Chief Operating Officer Brandon Smith added that CYTOPE was publicly disclosed only in November and said Prothena had already established research collaborations and was in discussions on broader applications across therapeutic areas.
Prothena also discussed its anti-amyloid beta antibody program. Dolan reviewed prior phase 1 ASCENT results for PRX012, including interim data showing mean amyloid PET reductions to approximately 27.5 centiloids at month 12 in patients dosed monthly subcutaneously at 400 mg from study start, and preliminary 18-month observations showing a mean reduction to approximately 60 centiloids, with 9 of 12 patients achieving amyloid negativity (centiloid value <24.1). However, management said ARIA-E rates for PRX012 were “non-competitive” relative to FDA-approved anti-A? antibodies, prompting the company to advance a PRX012 transferrin receptor program (PRX012-TfR) in preclinical development and explore partnership interest.
2025 results and 2026 guidance emphasize reduced cash use
Nguyen said 2025 results were in line or favorable to guidance. Prothena reported net cash used in operating and investing activities of $163.7 million (favorable to a $170 million to $178 million guidance range) and a net loss of $244.1 million (within a $240 million to $248 million range). As of year-end 2025, the company had $308.4 million in cash, cash equivalents, and restricted cash, and Nguyen said the company had 0 debt. As of Feb. 12, 2026, Prothena had 53.8 million ordinary shares outstanding.
For 2026, Prothena guided to $50 million to $55 million in net cash used in operating and investing activities and expects to end the year with about $255 million in cash, cash equivalents, and restricted cash (midpoint). Nguyen said the outlook is primarily driven by an expected net loss of $67 million to $72 million, including about $24 million of non-cash share-based compensation.
Management also reiterated that 2026 guidance does not include up to $105 million of potential aggregate clinical milestone payments tied to coramitug and a potential PRX019 advancement decision.
Kinney said Prothena received approvals needed for a share redemption program in 2026, including shareholder approval at an extraordinary general meeting and confirmation by the Irish High Court, and he said the company expects to implement the program this year and provide further announcements closer to its Form 10-K filing.
Looking ahead, management framed 2026 and 2027 as milestone years for business development and disclosures, citing additional scientific presentations for CYTOPE, potential partner milestones in 2026, and the anticipated completion of BMS’s TargetTau-1 phase 2 study in the first half of 2027.
About Prothena (NASDAQ:PRTA)
Prothena Corporation plc is a clinical-stage biotechnology company dedicated to the discovery and development of novel therapies for neurodegenerative and rare diseases driven by misfolded proteins. The company’s research focuses on immunotherapies and small molecules designed to target and clear disease-causing protein aggregates. Prothena leverages proprietary protein engineering and antibody discovery platforms to advance candidates through preclinical and clinical stages.
The company’s most advanced program is an antibody targeting aggregated alpha-synuclein for the potential treatment of Parkinson’s disease, currently in mid-stage clinical trials.
