Prothena Corporation plc

are in a 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, then zero, and a coordinator will be happy to assist you. I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at Perthena. Please proceed.

Thank you operator. Good afternoon and everyone and welcome to today's call to review Procena's business progress, fourth quarter and full year 2023 financial results and 2024 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 our investor website events and presentation section. On today's call, Dr. Gene Kinney, our President and Chief Executive Officer, will provide opening remarks, including an overview of Prothena's corporate and development strategy. Then Brandon Smith, our Chief Operating Officer, will provide an update on our pre-commercial progress for our wholly-owned Britannimab program, which is in phase three for the treatment of patients with Mayo stage four ALN mitosis. Dr. Hideki Garan, our Chief Medical Officer, will provide an update on our ongoing clinical programs. John Nguyen, our Chief Financial Officer and Chief Strategy Officer, will then discuss our 2023 financial results and 2024 financial guidance before turning it back to Gene 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 statement. 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 to review our 2023 financial results and business highlights. Let's begin on slide five. Our mission at Prothena is to create transformational therapies addressing significant unmet medical needs for the millions of patients and their loved ones that are affected by devastating 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. We continue to advance our mission, which has fueled our robust late-stage clinical pipeline, moving us closer to becoming a fully integrated commercial biotechnology company. 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 includes four wholly-owned programs and five partner programs. This intentional mix allows us to advance a fulsome portfolio by leveraging the benefits of working with key strategic partners on some programs while still maintaining the full upside potential for our wholly-owned programs where we feel that we have unique insights and expertise. I'll discuss four of our ongoing clinical programs on the next slide, PRX12, Pertamumab, Presinezumab, and NNC6019. But first, I'd like to highlight the exciting progress across our earlier stage programs. In July of 2023, we presented compelling preclinical results in a late-breaker poster presentation at AAIC for PRX123, our dual A-beta-tau vaccine program. And by year-end 2023, PRX123 received IND clearance and fast-track designation from the FDA. Our ongoing neuroscience R&D collaboration with BMS made meaningful advancements in 2023 and into this year. 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 of tau. In 2023, BMS opted into the global rights for this program with an additional milestone payment of $55 million and announced that the Phase 1 data supports advancing the program into a Phase 2 clinical trial in 2024. And for PRX19, a potential best-in-class antibody for the treatment of neurodegenerative diseases, we recently received FDA clearance for the IND application for this program as well. This is the second of three programs in our BMS collaboration. We remain well-funded to execute on our strategic objectives, taking us well beyond our upcoming clinical readout. As you will hear about in more detail later in this call, we ended 2023 with a strong cash position of $621 million. Moving now to slide seven. Our clinical expertise and differentiated approach enables us to advance best-in-class and or first-in-class therapies that have the potential to transform the treatment landscape for protein dysregulation diseases. Today, I'd like to focus on the four clinical programs that are nearing significant inflection points within the next 12 to 18 months. First, I'll discuss our wholly-owned programs, PRX12 and Bertamamab, and then move on to our partnered programs, Pracinezumab with Roche and NNC6019 with NovoNordisk. Pier X-12 is our next generation investigational treatment for Alzheimer's disease, which targets a key epitope at the amino terminus of amyloid beta with high binding potency. Pier X-12 was designed with the patient in mind, and we believe it has the potential to be best in class, transforming the treatment of Alzheimer's disease by meaningfully reducing treatment burden associated with the currently available anti-beta therapies. Based on our market research, We understand that a treatment with similar efficacy and safety to currently approved anti-beta therapies, but delivered as a once-monthly at-home subcutaneous treatment, has potential to be the dominant player in the market. In 2023, we presented compelling preclinical data at ADPD and at AAIC, demonstrating that PRX12 binds to amyloid plaques with high avidity. PRX12 is currently being evaluated in a double-blind placebo-controlled phase 1 trial. with the goal of identifying an optimal dose level or levels for a registration-enabling trial. The preclinical data, combined with the initial clinical data from our ongoing phase one trial, are supportive of a once-monthly subcutaneous treatment with a potential best-in-class profile. Pertamumab seeks to address the high risk of early mortality that remains an urgent unmet medical need for patients with Mayo Stage 4 AL amyloidosis. through its differentiated depleter mechanism, which is designed to clear accumulated amyloid and neutralize toxic light chain aggregates that are thought to cause organ dysfunction and failure. We are conducting the confirmatory phase three of FIRM-AL clinical trial, evaluating for Tamumab in patients with Mayo Stage 4 AL amyloid doses under a special protocol assessment or SPA agreement with the FDA with a primary endpoint of all-cause mortality at an unprecedented significance level of 0.10. We expect top-line results between the fourth quarter of 2024 and the second quarter of 2025. Pracinezumab is an antibody for the potential treatment of Parkinson's disease, designed to target a key epitope within the C-terminus of alpha-synuclein, and is the focus of a worldwide collaboration with Roche. Roche is currently conducting the Phase IIb Padova clinical trial in patients with early Parkinson's disease. Roche completed enrollment of this trial in the first quarter of 2023 and expects to report top line data later this year. And finally, NNC6019 is an amyloid depleter antibody for the potential treatment of ATTR cardiomyopathy. Novo Nordisk is currently conducting an ongoing phase two signal detection trial in patients with ATTR cardiomyopathy. The trial has fully recruited its patients with top-line results expected in the first half of next year. This is an exciting year of clinical trial execution for both Profina and our strategic partners. As we look ahead, we are also thoughtfully building out our commercial leadership and market insights for Bercamimab. So, to provide a little more context on our pre-commercial efforts, I will now turn the call over to Brandon. Brandon?