Prothena Advances Pipeline, Hides $105M Milestone Upside

Date of Call: Feb 19, 2026

Guidance:

• Full year 2026 net cash used in operating and investing activities expected between $50 million and $55 million.
• Expect to end 2026 with approximately $255 million in cash, cash equivalents, and restricted cash.
• Estimated net loss for 2026 between $67 million and $72 million, including $24 million of noncash share-based compensation.
• Guidance does not include up to $105 million in potential aggregate clinical milestone payments from partners in 2026.

Business Commentary:

Clinical Pipeline Progress:

• Prothena advanced two partner programs, prasinezumab and coramitug, into Phase III clinical trials in 2025. Roche initiated the PARAISO trial with approximately 900 participants with early Parkinson's disease, while Novo Nordisk started the CLEOPATTRA trial with about 1,280 patients with amyloid transthyretin cardiomyopathy.
• This progress was driven by consistent results from Phase II trials that demonstrated slowing of disease progression and positive outcomes in key endpoints like NT-proBNP and echocardiogram changes.

Financial Position and Milestones:

• Prothena reported a net cash position of $308.4 million as of December 31, 2025, which was favorable compared to their guidance. They anticipate net cash usage between $50 million and $55 million for 2026.
• The strong financial position is attributed to prudent capital utilization and potential milestone payments from partnerships, which support future clinical developments and capitalization efforts.

Preclinical and Technological Advancements:

• Prothena introduced CYTOPE technology, which shows potential in targeting intracellular disease pathways, specifically demonstrated in their TDP-43 CYTOPE program for ALS.
• The technology aims to address previously undruggable targets by enabling precise intracellular targeting, with preclinical studies indicating the ability to degrade phosphorylated TDP-43 aggregates.

Partnership and Strategic Priorities:

• Prothena has potential to earn up to $105 million in clinical milestone payments in 2026 if coramitug and PRX019 meet certain development targets.
• The strategic focus is on capturing value from clinical partnerships, implementing a share redemption program, and advancing preclinical portfolios to support future licensing and research collaborations.

Sentiment Analysis:

Overall Tone: Positive

• CEO Gene Kinney highlighted 'significant progress' with clinical pipeline, being 'well capitalized' with $308.4 million cash, and setting up an 'exciting future.' Management emphasized robust pipeline, potential milestones, and value creation, with statements like 'I'm proud of Prothena's execution and resilience in 2025.'

Q&A:

• Question from Shannon (Piper Sandler): Could you walk us through key milestones for partnered programs in 2026/2027 and what they might be contingent on?
  Response: Expect to share more CYTOPE data via presentations; BMS Phase II TargetTau-1 trial completion in H1 2027; potential $105M clinical milestones in 2026; share redemption program implementation.

• Question from Michael DiFiore (Evercore ISI): How do you keep the amyloid data story alive vs. larger competitors, and what makes an ideal transferrin receptor platform?
  Response: PRX012 shows strong amyloid removal with once-monthly subcutaneous dosing; adding transferrin technology (like in trontinemab) may improve ARIA-E profile. BD interest is active, especially for presymptomatic Alzheimer's applications.

• Question from Alexa Deemer (Cantor Fitzgerald): For the PRX019 Phase I study, do you plan to share data this year, and what would advance the program?
  Response: Data will be shared with partner BMS upon completion; decision to advance to Phase II and earn milestone payments will be up to BMS.

• Question from Jason Butler (Citizens JMP Securities): How much data is needed to secure a partnership for the CYTOPE platform, or to advance a program into clinic?
  Response: TDP-43 CYTOPE data shows robust intracellular targeting in ALS models, addressing both gain and loss of function. Technology is broadly applicable; active research collaborations are being established to derisk future partnerships.

• Question from Nevin Varghese (RBC Capital Markets): What is the mechanistic hypothesis for transferrin reducing ARIA risk, and would PRX012-TfR still be subcutaneously delivered?
  Response: Hypotheses include transferrin-mediated entry via capillaries reducing amyloid dwell time in vasculature. Subcutaneous administration remains viable for PRX012-TfR; higher potency may allow lower dosing to potentially minimize non-ARIA AEs.

Contradiction Point 1

Commercialization Timeline and Strategy for Birtamimab

It involves a change in the planned launch timeline for a key product, affecting investor expectations regarding market entry and revenue potential.

What is the question from Yasmeen Rahimi of Piper Sandler? - Shannon (on behalf of Yasmeen Rahimi, Piper Sandler)

2025Q4: The company sees these (PARAISO and CLEOPATRA trials) as high-unmet-need areas with significant economic potential. - Gene G. Kinney(CEO)

What are the key milestones for 2026 and 2027, and their dependencies, given PARAISO and CLEOPATRA trials won't complete until 2029? - Emma Seymour (Piper Sandler)

2024Q4: It is designed for a rare disease... Prothena plans to independently commercialize in the U.S. with a launch targeted for the second half of 2026. - Brandon Smith(COO)

Contradiction Point 2

Partnership and Data Sharing Expectations for PRX019

It involves a change in who controls data dissemination, impacting strategic partnerships and investor expectations for program progression.

What were the key takeaways from Alexa Deemer's earnings call at Cantor Fitzgerald? - Alexa Deemer (Cantor Fitzgerald)

2025Q4: Data will be shared with BMS upon completion. Bristol Myers Squibb has global rights to the program and will decide on data dissemination. Prothena will announce if they earn and are advanced into further development... - Gene G. Kinney(CEO) and Tran Nguyen(CFO)

Will data from the PRX019 Phase I trial (expected completion in 2026) be shared this year, and what are the key milestones for advancing the program? - Jason Butler (Citizens JMP Securities)

2024Q4: The focus is on confirming the efficacy and safety profile... Initial data around mid-2025 will come from the first 5A cohorts (≈225 patients) of the Phase 1/2 ASCENT-2 trial... The goal is to build a profile that addresses treatment burden while delivering efficacy. - Gene Kinney(CEO) and Mark Johnson(VP, Investor Relations)

Contradiction Point 3

Interpretation and Significance of ARIA Risk Data

It involves a change in the interpretation of a key safety finding, affecting the perceived risk profile and potential regulatory path for a program.

What were the key takeaways from Nevin Varghese's RBC Capital Markets earnings call? - Nevin Varghese (RBC Capital Markets)

2025Q4: Potential mechanisms for reduced ARIA risk with transferrin... This comprehensive approach will help define the safety and efficacy profile needed for future development. - Gene G. Kinney(CEO) and Chad Swanson(CMO)

What is the mechanistic hypothesis for how transferrin modification reduces ARIA risk, and do you expect lower hematological toxicities and potential effects on subcutaneous delivery? - Michael Yee (Jefferies)

2023Q4: The reported ARIA consistency with placebo... provides the basis for continuing dose escalation up to 400 mg. The Phase I trial is designed to explore this full range and define the safety profile needed to support a best-in-class claim. - Gene G. Kinney(CEO)

Contradiction Point 4

Development Timeline and Data Readout for PRX012

It involves a change in the expected timing for key data presentations, affecting investor expectations for program advancement and regulatory submissions.

Shannon for Yasmeen Rahimi, Piper Sandler? - Shannon (on behalf of Yasmeen Rahimi, Piper Sandler)

2025Q4: In 2026, Prothena expects to: Share more data from preclinical CYTOPE technology... In early 2027, Bristol Myers Squibb's Phase II TargetTau-1 trial... results expected in the first half of 2027. - Gene G. Kinney(CEO)

With primary completion expected in 2029 for the PARAISO and CLEOPATRA trials, could you outline key 2026 and 2027 milestones and their dependencies? - Charles Duncan (Cantor Fitzgerald)

2023Q4: An update for 2024 is planned, but the specific content (timing vs. data) is still to be determined. - Gene G. Kinney(CEO) and Hideki Garren(CMO)

Contradiction Point 5

Timeline and Control for Disseminating Phase I Clinical Data

It involves a change in the control and timing for releasing clinical data, impacting transparency and partnership dynamics.

Alexa Deemer (Cantor Fitzgerald)? - Alexa Deemer (Cantor Fitzgerald)

2025Q4: The PRX019 study is conducted by Prothena for its partner Bristol Myers Squibb. Data will be shared with BMS upon completion. Bristol Myers Squibb has global rights to the program and will decide on data dissemination. - Gene G. Kinney(CFO), Tran Nguyen(CFO)

For the PRX019 Phase I trial (expected 2026 completion), will data be shared this year, and what milestones are needed to advance the program? - Christopher Marai (Numora)

2017Q4: The PRONTO top-line results will be communicated as quickly as possible upon availability, including primary and secondary endpoints, as well as safety/tolerability data. - Dr. Gene Kinney(CEO)