Prothena Corporation plc

Good day, ladies and gentlemen, and welcome to the Procena Biosciences fourth quarter and full year 2025 Financial Results Conference Call. My name is Jeanne, and I will be your coordinator for today. At this time, all participants are in listen-only mode. We will be facilitating a question-and-answer session at the end of today's call. If at any time during the call you require assistance, please press star followed by zero, and a coordinator will be happy to assist you. I would now like to turn the presentation over to Mark Johnson, Vice President and Head of Investor Relations at Prothena. Please proceed.

Thank you, operator. Good afternoon, everyone, and welcome to today's call to review Prothena's business progress, fourth quarter and full year 2025 financial results, and 2026 financial guidance. Please review the press release we issued earlier today, which is available on our website at Prothena.com. and is also attached to a Form 8-K filed today with the SEC. In addition, we are using supplemental slides, which are available on our investor's website, events, and presentation section. On today's call, Dr. Gene Kinney, our President and Executive Officer, will provide opening remarks, including an overview on Prothena's corporate strategy. Chad Swanson, our Chief Development Officer, will provide an update on our ongoing partner clinical programs. And Phil Dolan, our vice president and head of discovery research, will provide an update on our active preclinical program. Tron Nguyen, our chief strategy officer and chief financial officer, will then discuss our 2025 financial results and 2026 financial guidance before turning it back to Jean for closing remarks, at which point we will open up the call for a Q&A session. Brandon Smith, our chief operating officer, will also be available during the Q&A session. Before we begin, I would like to remind you that during today's presentation, we will be making forward-looking statements that are subject to certain risks, uncertainties, and other factors that could cause actual results to differ materially from those reported to you in any of the forward-looking statements. For discussion of these risks and uncertainties associated with our forward-looking statements, please see our press release issued today, as well as our most recent filings with the SEC and our annual report on Form 10-K to be filed with the SEC for our fiscal year 2025. We disclaim any obligation to update our forward-looking statements. With that, I'd like to turn the call over to Gene.

Thank you, Mark, and thank you all for joining us today. Let's begin on slide five. In 2025, we saw significant progress with our clinical pipeline, where two of our partner programs, Presonizumab and Gramatug, advanced into Phase III clinical trials. Roche advanced Presonizumab into the Phase III RECO trial, evaluating 900 participants with early Parkinson's disease. This decision was informed by results from two Phase II clinical trials that both demonstrated consistent flowing of disease progression. Novo Nordisk advanced Caramatug into the Phase III Cleopatra trial, evaluating 1,280 patients with amyloid transcylarectin cardiomyopathy, or ATTRCM. This decision was informed by results from their Phase II trial demonstrating positive NT-proBNP and echocardiogram changes, as well as directional observation of benefit in the six-minute walk test. Our collaborations with Bristol-Myers Squibb also progressed in 2025 with several important advancements, including the Phase II Target TAL-1 clinical trial, evaluating BMS 986446 in early Alzheimer's disease, which was fully enrolled in 2025 with completion expected in the first half of 2027. Bristol-Myers Squibb also completed a phase one study evaluating a subcutaneous formulation of BMS 986446 in 2025. And BMS 986446 obtained fast track designation from the US FDA for the treatment of Alzheimer's disease. And finally, we are conducting a phase one trial for PRX19, which is on track for completion in 2026. We also shared important updates from our wholly owned preclinical portfolio in 2025. In the fourth quarter, we introduced our CyTOPE technology with presentations of our TDP43 CyTOPE program for ALS at two scientific congresses. At a high level, these data demonstrated that our CyTOPE technology has the potential to enable precise targeting of intracellular disease pathways. We also reported results from our Phase I Ascent clinical program evaluating PRX12 in patients with early Alzheimer's disease. The results helped to elucidate the profile of this once-monthly subcutaneous anti-A-beta antibody. Based on significant scientific advances over the last several years, we believe we can further improve this profile with the addition of transparent receptor technology and are actively advancing a PRX12 transparent program in preclinical development. Turning to slide six, we have several key 2026 priorities that we believe meaningfully contribute to long-term value creation. The first is to ensure we are best positioned to capture value embedded in our clinical partnerships. As a reminder, all of our partnerships with large pharma companies are programs that originated from Prathena's R&D engine. This year, we have the potential to earn up to $105 million an aggregate clinical milestone payment, if Karama Tug achieves a pre-specified enrollment target in its ongoing phase three trial, and if BMS decides to advance PRX-19 into phase two clinical development. In addition, we have now received all the necessary approvals from our extraordinary general meeting of shareholders and confirmed by the Irish High Court to support a share redemption program in 2026. Finally, we continue to advance our knowledge and understanding of our preclinical portfolio to support our business development team as they explore research collaborations and licensing agreements. For example, we are engaged in a research collaboration with a large pharmaceutical company that explores multiple approaches for applying our CyTOPE technology to advance and elucidate intracellular targeting. We look forward to establishing additional research collaborations, which may lead to future licensing deals. Our strategic priorities are supported by our $308.4 million cash and restricted cash balance as of year end 2025, and our prudent capital utilization to ensure that we are well positioned to receive future potential economics from our partner programs. Let's move to slide seven to review our upcoming catalysts from our partner portfolio. Looking ahead, we have two potential milestones in 2026 from Karamatug and PRX19. which could be worth up to $105 million. In the first half of 2027, we expect Bristol-Myers Squibb to complete their phase two target TAL-1 trial for BMS 986446. And in 2029, we expect primary completion from the two phase three trials evaluating Roche's Pracinazumab and NovoNordisk's Grammaton. In total, when you look at our four partner clinical programs, They have the potential in aggregate to deliver up to approximately $3 billion in future milestone payments, which is in addition to any royalties. With that, I'll now turn the call over to Chad to discuss our partner programs in more detail.