Prothena Corporation plc

Ladies and gentlemen, thank you for standing by and welcome to Prothena's fourth quarter full year 2021 financial results conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press star one. We ask that you please limit yourself to one question. Thank you. Jennifer Zabuda, you may begin your conference.

Jennifer Zabuda Thank you, Operator. Good afternoon, everyone, and welcome to Prothena's investor conference call to review our business progress, our fourth quarter and full year 2021 financial results, and 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. On today's call, Dr. Jean Kinney, our President and Chief Executive Officer, will highlight Provena's progress across our portfolio in 2021, as well as our organizational evolution as we continue advancing towards becoming a fully integrated biotechnology company. Following Jean's comments, Tran Nguyen, our Chief Financial Officer and Chief Strategy Officer, will review our financial results and performance for the fourth quarter and full year of 2021 and will provide our 2022 financial guidance before turning it back to Jean for closing remarks. We will then open the call for Q&A and be joined by Dr. Hideki Garan, our Chief Medical Officer, and Dr. Wagner Zago, our Chief Scientific Officer. 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 a 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. And with that, I'd like to turn the call over to Gene.

Thank you, Jen, and thank you all for joining us to review our 2021 financial results and business highlights. 2021 was a productive year for Prothena, marked by meaningful progress in our R&D portfolio, which represents the culmination of multi-year efforts. We're hopeful that these efforts will soon lead to impactful treatments for the millions of patients and families that are affected by diseases caused by misfolded proteins. In 2021, we also continued to attract and retain highly talented professionals with excellent track records to support our transition towards becoming a fully integrated biotechnology company. Additionally, we ended the year with a strong cash position, which included $200 million in partner payments from our collaborations with leading pharmaceutical organizations, including Bristol-Myers Squibb, Novo Nordisk, and Roche. These collaborations are part of an intentional mix of wholly owned and partnered assets, which allows us to have a broad pipeline with blockbuster potential, further supporting our growth as a company. Patina is driven by our mission to make a real impact for the patients and families we serve. That mission is enabled by our deep scientific expertise in protein dysregulation, which serves as a unifying thread between our business strategy, our portfolio development, and the dedication that propels our team every day. We believe that our focus on slowing, stopping, and treating neurodegenerative and rare peripheral amyloid diseases addresses significant unmet medical needs where our biology-directed engine, our clinical expertise, and our market positioning will enable us to advance best-in-class therapies that have the potential to transform the lives of patients. Our focus on neurodegenerative diseases includes Alzheimer's and Parkinson's, which sadly are growing exponentially. Combined, these two diseases affect an estimated 60 million people globally today. The significant burden is not only experienced by patients, but also by caregivers and the overall healthcare system. In rare peripheral amyloid diseases, Bertamumab and PRX4 are being developed in targeted patient populations at high risk for early mortality, which underscores our strategy to develop therapies for patients with an urgent need for improved survival. Since our inception, our core guiding principle has been to follow the science empirically and without bias. This rigorous approach to the advancement of medicine allows us to discover underlying pathophysiological processes and design molecules that optimally target pathogenic proteins and consequently have the greatest probability to slow or prevent disease. Over the years, we have refined our approach to include what we believe is an unparalleled knowledge of disease pathology and expertise in empirical epitope mapping, advancing only those molecules that show robust and consistent biological effect in the reduction of disease. Using our unique biology-directed engine, which leverages our deep know-how, today we've been able to advance three programs into mid to late clinical stages, and six discovery candidates toward the clinic, with five potential new INDs projected by 2026. Praveena's understanding of protein dysregulation is based on many decades of scientific discoveries in the field. Much of our team, including Wagner, our chief scientific officer, who's on the call today, have contributed key scientific and clinical discoveries in our field and have built a scientific heritage within Prathena that allows for an informed approach for the development of potentially best-in-class therapeutic candidates. Last year, we continued to add to this deep scientific heritage with the addition of key personnel, such as Hideki, our chief medical officer, who is also present on our call today. Before we dive into the progress we made this year, I wanted to take a moment to highlight the breakthroughs that we as a field have made in advancing treatments for Alzheimer's disease. 2021 was a milestone year for the Alzheimer's community. Notable developments included the FDA accelerated approval of the first disease-modifying therapy, significant advancements in clinical study design, including optimized patient selection strategies, advancements in the use of biomarkers, including blood-based biomarkers, an increased prominence of IADRS as a clinical outcome measure, and a growing amount of evidence generated across multiple clinical data sets confirming the benefit of anti-data therapies that interact with the immunoterminists of that target. This progress stands on the shoulders of many great scientists, including Prathena's late co-founder, Dr. Dale Shank, and multiple Prothena scientists who carefully observe and follow the iterative scientific and clinical trial design learnings to bring forth this new class of therapy to patients with Alzheimer's disease. At Prothena, we have celebrated these advancements, but also believe that further improvement is needed. This is why we are advancing what we believe is one of the most comprehensive therapeutic strategies to treat Alzheimer's disease. We've developed three product candidates targeting key pathological pathways of the disease cascade, which expand from next-generation potentially disease-modifying treatment to potential combination and prevention strategies. Our portfolio takes advantage of the scientific and clinical trial design advances and positions Prathena as a leader in the transformation of Alzheimer's therapeutic approaches. With that, let me now focus on highlighting some of the progress made across the portfolio in 2021. I'll start with PRX12, a potential best-in-class, patient-friendly, subcutaneous delivery treatment for Alzheimer's disease, targeting a key epitope at the immunoterminus of amyloid beta with high binding potency. To date, preclinical data have shown that PRX12 binds to amyloid plaques with high avidity, consistent with the potential for more effective A-beta plaque clearance at substantially lower doses than approved anti-A-beta therapies. New preclinical data presented at the Alzheimer's Association International Conference, or AAIC, this past summer demonstrated that PRX12 significantly cleared both pyroglutamate-modified and unmodified A-beta plaque in brain tissue at concentrations that are expected to be reached in the CNS with subcutaneous administration on a convenient treatment schedule. We believe that PRX12 has the potential to transform the field of Alzheimer's disease Our goal with PRX12 is to offer greater patient accessibility and compliance relative to the approved therapy and other immunoterminous targeted treatments currently under development. Compared to first-generation treatments, subcutaneous PRX12 is also expected to result in smaller fluctuations in brain antibody concentration. This feature may allow us to differentiate on both efficacy and safety endpoints. Because of its high binding potency and suitability for subcutaneous administration, PRX12 has the potential to serve as a foundational anti-ABETA treatment for patients with Alzheimer's disease. We intend to fully leverage the learnings from upcoming clinical, regulatory, and commercial milestones from other first-generation anti-ABETA therapies to maximize the probability of success for our PRX12 program. In 2021, we also brought our tau-targeting monoclonal antibody, PRX5, into the clinic. PRX5 is designed to be a best-in-class anti-tau antibody by specifically targeting an epitope within the microtubule binding region, or MTBR. Tau tangles, along with amyloid beta plaques, are pathological hallmarks of Alzheimer's disease. and research indicates that tau pathology is related to the clinical and cognitive decline associated with disease. By leveraging our unbiased, biology-directed engine, we found that targeting specific regions within the MTBR resulted in more consistent and robust reduction in the pathogenic uptake of tau into neurons and the downstream neurotoxic effects. With diseases, or ADPD, in March of last year, we presented new preclinical data showcasing pathology and downstream behavioral deficits in multiple in vitro and preclinical in vivo models. PRX-5 is one of three programs being developed in partnership with our colleagues at Bristol Myers Squibb and for which we received an $80 million option payment in 2021. We also advanced a third Alzheimer's program, our dual A-beta-Tau vaccine, from discovery to preclinical development in 2021. For the first time, we presented data at AAIC on our dual A-beta-Tau active vaccine. This vaccine is a multi-epitope, single-agent vaccine designed to target the two key pathologies associated with Alzheimer's disease. Our data showed that vaccination of mice and primates generated a robust