Prothena Corporation plc

My name is Pam, 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 towards 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 call over to Mark Johnson, Vice President at Prisina. Please proceed.

Thank you. Good afternoon, everyone, and welcome to today's call to review Procena's business progress, fourth quarter and full year 2024 financial results, and 2025 financial guidance. Please review the press release we issued earlier today, which is available on our website at procena.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 the Invent and Presentation section of our Investor Relations website. On today's call, Dr. Jean Kenney, our President and Chief Executive Officer, will provide opening remarks, including an overview of Prothena's corporate and development strategy. Chad Swanson, our Chief Development Officer, will provide an update on our ongoing wholly owned clinical program. And Brandon Smith, our Chief Operating Officer, will provide commercial insights on those programs. Tron Nguyen. Our Chief Financial Officer and Chief Strategy Officer will then discuss our 2024 financial results and 2025 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. 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 referred to in any forward-looking statements. For discussion of the 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. 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. Our mission at Prathena is to create transformational therapies addressing significant unmet medical needs for the millions of patients and their loved ones that are affected by devastating life-threatening diseases caused by protein dysregulation. That mission is enabled by our deep scientific expertise, which serves as a unifying thread connecting our corporate strategy, our portfolio development, and the dedication that propels Prothenians every day. As a result of our commitment to our mission, we have created a robust portfolio of therapeutic drug candidates targeting both neurodegenerative and rare peripheral amyloid diseases as shown on slide six. Our portfolio has four wholly owned and four partner programs across late to mid to early stages of clinical development. This intentional mix allows us to leverage the benefits of working with key strategic partners to rapidly advance these treatments to patients while maintaining financial upside for Porcina. These partnerships further allow us to invest in the full upside potential of our wholly owned program advancing them further in development to potential commercialization. Moving to slide seven. Our wholly owned clinical programs are nearing significant inflection points in 2025, setting up a transformational year for Prothenib. Pertamamab is currently the only potential treatment for AL amyloidosis that has demonstrated an early survival benefit in a randomized clinical trial. The survival data from our prior phase three vital trials enables us to receive a special protocol assessment or SPA agreement with the FDA to confirm these results in our ongoing phase three AFIRM-AL trial at an unprecedented statistical significance level of 0.10. The primary endpoint in AFIRM-AL is time to all cause mortality, and we expect to announce top line results in the second quarter of this year. If positive at a p-value equal to or less than 0.1, we would expect to submit a BLA to the FDA for potential US launch by the second half of 2026. Percanumab represents a very attractive potential multi-billion dollar global commercial opportunity. This is a rare disease patient population primarily treated by hematologists in amyloidosis specialty centers for which the ongoing Bertamumab program is designed to address the significant unmet need of early mortality. In addition, our Alzheimer's disease portfolio, PRX12 and PRX123, includes unique programs designed to address the unmet need of the millions of pre-symptomatic and early symptomatic AD patients and their families. PRX-12 is our anti-A-beta program designed to be a single-injection, once-monthly, subcutaneous treatment to alleviate treatment burden and improve access with an easy-to-use at-home administration. Around mid-year 2025, we expect to announce initial results from our ongoing Phase I ASCENT clinical trials evaluating PRX-12 in early Alzheimer's patients with additional data updates throughout the year. Chad will describe the trial. and read out in more detail later in his presentation. In addition, our PRX123 dual anti-A-beta and anti-Cal vaccine has been granted fast track designation and has an IMD cleared by the FDA. That will describe our confidence in this program and potential next steps as well. Moving on to slide eight. We have four ongoing clinical partnerships with large pharmaceutical companies, enabling us to leverage external resources and expertise to further advance potentially transformative medicine patients and create long-term value for Prothenib. Prothenizumab is being investigated as a potential treatment for early Parkinson's disease. And our partner, Roche, announced top-line results from the Phase IIb Padova study in December of 2024. The PEDOVA phase 2B trial evaluated 586 people with early Parkinson's for a minimum 18 months while on stable symptomatic treatment. In the study, presenizumab showed a potential clinical effect in the primary endpoint of time to confirmed mode of progression with a hazard ratio of 0.84 and narrowly missed statistical significance with a p-value of 0.0657. The effect of prasinezumab was more pronounced in a pre-specified analysis in the approximately 75% of participants treated with levodopa with a hazard ratio of 0.79 and a nominal p-value of 0.0431. In pre-specified supplementary covariate adjusted analyses of these endpoints, the effects were even more pronounced and all nominally statistically significant. Consistent positive trends across multiple secondary and exploratory endpoints were also observed, and presenazumab continued to be well-tolerated. The Phase IIb PEDOVA results, along with prior clinical study results, support further clinical development of presenazumab as a potential first-in-class disease-modifying treatment for patients with Parkinson's disease. Roche is continuing to evaluate the effects of presenazumab in open-label extension studies from both the Phase II Pasadena and the Phase IIb Padova trials. Roche will continue to evaluate the data and work together with health authorities to determine next steps. Moving on to Caramatog, an anti-amyloid antibody for the potential treatment of ATTR amyloidosis with cardiomyopathy, or ATTR-CM. Novo Nordisk is currently conducting a Phase II signal detection trial in approximately 99 patients with ATTR-CM. The trial should complete in the first half of 2025, and we expect Novo to announce results and potential next steps in the second half of 2025. We look forward to future updates from Novo, including potential further clinical development of parambutans, moving this important new treatment closer to patients. We made significant progress in 2024 with our two-partner clinical programs with Bristol-Myers Squibb. BMS 986446, formerly PRX005, is a potential best-in-class antibody for the treatment of Alzheimer's disease that specifically targets a key epitope within the microtubule binding region, or MTBR, of tau. In 2024, BMS initiated the 475-patient target tau1 Phase 2 trial. The trial is evaluating placebo versus low and high doses of BMS 986446 in patients with early Alzheimer's disease. The primary endpoints have changed from baseline, and the clinical dementia rating scales from a box to score at 18 months. Enrollment is ongoing, and the trial is expected to complete in 2027. Also in 2024, BMS opted into a global license agreement for PRX-19, which included a payment of $80 million. As part of the agreement, Perthena has initiated a phase one first in human clinical trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of single ascending and multiple doses in healthy adults. The trial is enrolling and expected to complete in 2026. This is an exciting year for Prathena and our strategic partners. To discuss our wholly-owned clinical programs in further detail, I will now turn the call over to Chad. Chad?