We disclaim any obligation to update our forward-looking statements. With that, I'd like to turn the call over to Gene.

Gene Kinney: 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 5. Our mission at Prothena 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 disregulation. That mission is enabled by our deep scientific expertise, which serves as a unifying trend connecting our corporate strategy, our portfolio development and the dedication that propels opinions 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 candidate targeting both neurodegenerative and rare peripheral amyloid diseases as shown on Slide 6. Our portfolio includes four wholly-owned programs and five partnered 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 insight and expertise. I'll discuss four of our ongoing clinical programs on the next Slide, PRX012, Birtamimab, Prasinezumab and NNC6019. But first I'd like to highlight the exciting progress across our earlier-stage program.

In July of 2023, we presented compelling preclinical results in a late breaker poster presentation at AAIC for PRx 1, 2, 3, our dual Aβ-tau vaccine program and by year-end 2023, PRX 123 received IND clearance and Fast Track designation from the FDA. Our own going Neuroscience R&D collaboration with CMS 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 the key episodes within the microtubule binding region of tau. In 2023, CMS 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 readouts. As you will hear about more detail later in this call, we ended 2023 with a strong cash position of $621 million. Moving now to Slide 7. 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 Birtamimab, and then move on to our partnered program Prasinezumab Roche and NNC6019 with Novo Nordisk. PRX12 is our next-generation investigational treatment for Alzheimer's disease, which targets the key epitope that the Amino Terminus of amyloid beta with high binding potency. PRX12 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 data 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 ADPD and AAIC demonstrating that PRX12 binds the 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 our registration enabling trial. The preclinical data combined with the initial clinical data from our ongoing Phase 1 trial are supportive of a once monthly, subcutaneous treatment with a potential best-in-class profile. Birtamimab seeks to address the high risk of early mortality that remains an urgent unmet medical need for patients with mayo stage IV AL Amyloidosis. Through its differentiated depleter mechanism, which is designed to clear accumulated amyloid and neutralized toxic light chain aggregates that are thought to cause organ dysfunction and failure.

We're conducting the confirmatory Phase AFFIRM AL clinical trial evaluating Birtamimab in patients with MAYO Stage IV Amyloidosis 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 second quarter of 2025. Prasinezumab 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 2b PADOVA clinical trial in patients with early Parkinson's disease. Roche completed enrollments 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 2 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 Prothena and our strategic partners. As we look ahead, we are also thoughtfully building out our commercial leadership and market insights for Birtamimab so to provide a little more context on our pre-commercial efforts, I will now turn the call over to Brandon. Brandon?

Brandon Smith: Thanks, Gene. Moving to Slide 9. As we continue to executing on our ongoing confirmatory Phase 3 of AFFIRM AL clinical trial, we are focused on building out our commercial capabilities to support Birtamimab as our first potential commercial product. Among patients with AL Amyloidosis are are progressive and fatal disease newly diagnosed individuals with significant cardiac involvement such as MAYO stage IV are at the highest risk for early mortality. This remains a serious unmet need for patients and their families. Birtamimab is the only candidate to have shown a survival benefit in patients with MAYO stage IV for AL Amyloidosis in a randomized clinical trial, our previous Phase 3 VITAL trial. The ongoing confirmatory AFFIRM AL trial was designed based on a SPA agreement with the FDA to approve Birtamimab at a p-value of less than or equal to 0.1 for the primary endpoint of all-cause mortality showing an early and sustained impact on mortality is a powerful differentiator and If approved we are confident that Birtamimab will be welcomed as a major advancement in the field and a key treatment option.

Moving to Slide 10. The market dynamics for Birtamimab as our potential first commercial product are quite compelling. Our plan is to independently commercialize Birtamimab and we believe that we will be able to efficiently reach prescribers for advanced patients with a focused commercial presence. This is a rare disease patient population with a targeted call point where hematologists with support from specialized cardiologists and a primary treating specialist. KOLs in the community at large recognized the urgent need for treatment that improved survival in patients with AL Amyloidosis who are at high risk for early mortality. Based on epidemiology studies we estimate there are over 20,000 patients with MAYO Stage IV AL Amyloidosis across the major markets including United States, Europe, China, Brazil and Japan.

This is further supported by our claims data analysis to identify patients who are actively receiving treatment for AL Amyloidosis in the United States. Based on this, we believe there are approximately 4,000 MAYO Stage IV patients in the U.S. In addition, our US and European market research indicates there are approximately 75% of patients are treated in approximately 500 centers of excellence and amyloidosis specialty centers usually within academic hospitals. Our team continues to build upon the existing relationships we've established for KOLs and experts in the field through our extensive clinical programs for Birtamimab. We will continue to collaborate with these KOLs and experts along with the organizations that publish treatment guidelines such as NCCN and the International Society of amyloidosis to ensure they are fully aware of and informed about Birtamimab.

This includes continued to present our data at top medical congresses and publications in peer-reviewed journals. Today, we are building our commercial leadership team thoughtfully as we prepare for launch. I'll now turn it over to Hideki to review our clinical programs.

Hideki Garren: Thank you, Brandon. Let's continue with Birtamimab and review the results for previous VITAL trial, which we’re publishing at ASH peer-reviewed Journal, Blood last year. Importantly, we observed a survival benefit in the subset of approximately 30% of patients who are categorized as a male stage IV bassline. The capital MAYO curve illustrating the separation is shown here on Slide 12 demonstrating an early and sustained benefits. In this high risk group, we observed the survival benefits facing Birtamimab reflecting approximately 60% relative reductions of all-cause mortality at a p-value of 0.021. This was further supported by meaningful and significant improvements in functions as measured by six-minute walk test and quality of life as measured by SF-36.

Turning to Slide 13, expand on Brandon's earlier remarks, based on our extensive analysis of VITAL data, as well as further confirmation of the data with external statistical experts and leading physicians in the field, we actively engage with the FDA to the line on the path towards regulatory success for Birtamimab. A SPA was agreed to between Prothena and the FDA with a confirmatory Phase 3 AFFIRM AL clinical trial to be conducted in patients with AL amyloidosis categorized as MAYO Stage 4 baseline with a pre agreed upon significance level of alpha less than or equal to zero point one zero on a primary endpoint of all-cause mortality. This is a time to event trial and patients are randomized two to one on Birtamimab as standard-of-care or placebo plus standard-of-care.

At the end of 2023, based on a predetermined number of mortality events, we were able to estimate that top-line results of but before Mayo would be available between the fourth quarter of 2024 and second quarter of 2025. We very much look forward to the results for this trial moving us one step closer to getting the treatment to patients and families in need. Let’s discuss PRX12 our potential best-in-class anti-amyloid beta treatment starting on Slide 14. We believe PRX12 could be a best-in-class anti amyloid beta treatment for early Alzheimer's disease in order to achieve this target product profile, we need to establish escapades convenience and safety. PRX12 was intentionally designed with the antibody attributes required to achieve a similar or better efficacy and safety profile to currently approved anti-immuno therapies.

With the clear differentiation as being administered in a much more convenient and accessible once monthly, at home, subcutaneous treatment. PRX12 is a humanized IgG1 monoclonal antibody designed to provide a longer half-life and improved anti-immuno treatments with low immunogenicity. We’ve demonstrated a high potent binding, high affinity and avidity and a slow off rate allowing for considered target engagement, all of which are optimal for once monthly subcutaneous treatment. The ongoing PRX12 stage 1 trial, which we would discuss on Slide 15 and 16 is designed to demonstrate a potential best-in-class profile into clinics. Moving the Slides 15, Phase 1 is a double-blind placebo-controlled single ascending dose clinical trial evaluating PRX12 in healthy volunteers and participants with early Alzheimer's disease.

The trial enrolled approximately eight participants per single ascending dose cohorts, randomized 3 to 1 to receive a single subcutaneous dose of PRX12 or placebo and doses ranging from 70 to 400 milligrams. Moving on to the multiple setting dose cohorts on Slide 16. Ascent 2 is our double blind placebo-controlled multiple ascending dose clinical trials evaluating PRX12 in people with early Alzheimer's disease. Each match cohort is randomized 3 to 1 to receive PRX12 or placebo once monthly as six months in multiple ascending dose levels. The objectives of the trial are twofold. One is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of PRX 12 in patients with early Alzheimer's disease. And two is to find the optimum dose level or levels for registration enabling clinical trial.

There are a couple of key aspects to the MAD trial design that I like to highlight today. Participants are assigned to two groups of cohorts based on APOε4 status which referred to as A cohort or B cohort. Participants in the A cohorts are either APOε4 non-carriers or heterozygous carriers. Each of these A cohorts is evaluating approximately 32 participants with early Alzheimer's disease and doses ranging from 45 to 400 milligrams. In addition, we are evaluating APOε4 homozygous carriers with separate B cohorts for approximately 12 participants with early Alzheimer's disease in doses ranging from 45 to 200 milligrams. Following the first six months, which is placebo-controlled, participants previously taking PRX12 of placebo are eligible to receive an additional six monthly doses of PRX12 in an open-label extension.

We've completed all cohorts and the double-blind portion of the initial 70 mg MAD A cohort, The Phase one clinical trial continues as planned as the initial data supports once monthly, subcutaneous treatment and dose escalation in additional cohorts. We look forward to evaluating the full exposure response relationship of PRX12 and expect to update you later this year. Turning now to Prasinezumab on Slide 17, Prasinezumab is the first Anti-alpha-synuclein antibody to demonstrate slowing the progression on measures of Parkinson's disease and Phase 2 trial. our partner Roche previously presented data from the phase two PASADENA trial showing Prasinezumab reduced one year motor progression by 35% as measured by the MDS-UPDRS Part III, a scale of motor dysfunction and comparison to placebo.

Roche continues to provide meaningful updates on the ongoing open-label extension clinical trial 12 including recently at the Movement Disorder Study Congress in August. Roche compares three year progression of motor science and the Prasinezumab population with a propensity score balance cohort of real-world data from the Parkinson's progression markers initiative or PPMI The Prasinezumab population saw 62% slowing progression as measured by the MDS-UPDRS Part III in the early start Prasinezumab population, as compared to the real world data cohort. These data continues to support Prasinezumab potential effects of delaying motor progression in Parkinson's disease. Roche has advanced Prasinezumab into the Phase 2b PADOVA trial, which is a double-blind placebo-controlled trials evaluating 586 patients with early Parkinson's disease.

Participants are randomized 1 to 1 to receive Prasinezumab or placebo every four weeks for at least 18 months. Roche announced they've completed enrollment in the first quarter of 2023. The primary endpoint is time to clinic meaningful professional or motor signs of the disease as assessed by a five point or greater increase in the MDS-UPDRS Part III from baseline. This disease progression may be correlated to a meaningful worsening on the clinical global pressure and fluid scale. Roche expects to report top-line data from the PADOVA trial later this year. Moving to NNC6019 on Slide 18 NNC6019 has been developed by Novo Nordisk as a potential first-in-class amyloid depleter antibody for the treatment of ATTR cardiomyopathy. This is a rare progressive and fatal disease characterized by deposition of abnormal non-native forms of TTR protein, and amyloid in vital organs.

NNC6019 is thought to deplete both deposited amyloid circulating non-native TTR to prevent further depositions to improve organ function. This mechanism of action has a potential benefit for ATTR patients at high risk for early mortality due to amyloid deposition in vital organs. Novo Nordisk is progressing this program an ongoing double-blind placebo-controlled signal detection Phase 2 clinical trial. The trial has completed recruitment and Novo estimates primary completion in the first half of 2025. And now I'd like to turn the call over to Tran Nguyen for a discussion of our 2022 financial performance and our 2024 financial guidance. Tran?

Tran Nguyen: Thanks, Hideki. Today, we reported financial results that were favorable to our 2023 financial guidance. Please refer to our press release for a detailed breakdown of our financial results. As Gene mentioned during his opening remarks, our robust portfolio of wholly-owned and strategically partnered programs allows us to leverage partner payments while still maintaining full upside potential of our wholly-owned programs. In 2023, BMS opted in to secure their global rights for the BMS 986446 formerly known as PRX5 for $55 million. In terms of our 2023 financial performance relative to guidance, we had net cash used in operating an investing activity of a $136.7 million, which was favorable to our guidance range of $148 million to $161 million.

Net loss was $147 million, which was favorable to our guidance range of a $153 million to $171 million. As of December 31st 2023, Prothena had $621 million in cash, cash equivalents and restricted cash which is favorable to our guidance of $600 million. As of February 9th 2024 Prothena had approximately 53.7 million ordinary shares outstanding. Additionally, we continue to have a simple capital structure with zero debt. Turning to our 2024 financial guidance that's on Slide 21. We expect our full year 2024 net cash used in operating and investing activities to be between $208 million and $225 million. We expect to end the year with approximately $405 million in cash, cash equivalents and restricted cash, which represents the midpoint of the range.

The estimated full year 2024 net cash used in operating and investing activities is primarily driven by an estimated net loss of $229 million to $255 million, which includes an estimated $51 million of non-cash share-based compensation expense. With that, I'll turn the call back over to Gene to discuss our upcoming milestones. Gene? Thanks, Tran. Moving to Slide 23. I'd like to acknowledge and thank the patients, their families, physicians and study site staff who participate in all our clinical trials. Without their support we could not elucidate the potential impacts of the new medicines we’re developing. I'd also like to thank our talented Prothenians for their ongoing commitment to advancing protein dysregulation science to make a real impact for the patients and families we serve.

As we look ahead, we're excited to have meaningful catalysts across our programs with potential clinical readouts from four ongoing clinical trials within the next 12 to 18 months, which include top-line results from our confirmatory AFFIRM AL Phase 3 trial evaluating Birtamimab in patients with MAYO stage IV AL amyloidosis, clinical data from our ongoing phase 1 trial evaluated PRX 12 as a potential best-in-class treatment in early Alzheimer's disease, top-line results from the Phase 2b PADOVA trial evaluating Prasinezumab for Parkinson's disease being conducted by Roche. And finally clinical data from the Phase 2 Signal Detection trial evaluating NNC6019 for the treatment of ATTR cardiomyopathy by Novo Nordisk. I am proud of the progress that Prothena made in 2023 and continued into 2024.

We are well-capitalized with a robust cash position and remain focused on advancing our clinical programs as we strive to become a fully integrated commercial biotechnology company. With that we will now open the call for Q&A. Operator?

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