Arrowhead Pharmaceuticals, Inc.

our Chief Financial Officer, will give a review of the financials. We will then open the call up to your questions. Before we begin, I would like to remind you the comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical fact are forward-looking that could cause actual results to differ materially from those expressed in any forward-looking statements. For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q. With that said, I'd like to turn the call over to Chris Anzalone, President and CEO of the company. Chris?

Thanks, Vince. Good afternoon, everyone, and thank you for joining us today. I want to start by thanking you, I want to start by saying thank you to all those who joined us yesterday in Verona, Wisconsin for the groundbreaking ceremony at the site of our new manufacturing and lab facilities, including Mayor Diaz, Secretary Hughes, and Governor Evers. Many people from BioForward, the local universities, the cities of Madison and Verona, and the state of Wisconsin have been very supportive of Arrowhead over the years. We appreciate their partnership as we grow our business and capabilities to support the potential future commercial opportunities for our investigational RNAi-based medicines. To that end, we announced yesterday that we received awards of up to $18.5 million in incentives to invest in the local region and create new jobs. These incentives help to defray some of the build-out costs for our Verona facility, but importantly, they demonstrate the commitment of the region to expand the number of highly skilled jobs and attract talent. We have been very impressed with the quality of the workforce and intend to be a longtime contributor to the growing biotech ecosystem in Wisconsin. So what does this new manufacturing facility and associated office and lab facility do for Arrowhead? First, it increases our control over manufacturing at all scales, which should decrease costs and increase our speed and flexibility. Second, it enables us to better control IP as we develop new methods of manufacturing aimed at decreasing costs and increasing purity and scale. Third, it makes us a better and more complete partner to those companies bringing the drugs we create to patients. And fourth, it provides additional specialized lab space to enable continued growth and innovation as we bring RNAi to new cell types and address new diseases. This is an investment in Arrowhead's future as a vertically integrated commercial stage pharmaceutical company. We are making this investment now because we have a high degree of confidence in our investigational medicines, both wholly owned and partnered. This is an important step when a development stage company is serious about becoming a commercial entity. Let's now talk about some of the recent progress we've made toward that transition. First, we initiated the Palisade study, Arrowhead's first Phase III study of AeroApoC3 in patients with familial chylomicronemia syndrome, or FCS. FCS is a rare disease in which patients have extraordinarily high triglyceride levels, often in the thousands of milligrams per deciliter. This can lead to severe and recurrent bouts of pancreatitis, which often involves hospitalization and can be fatal. In addition, these patients experience multiple additional symptoms which adversely impact quality of life. These patients have no FDA-approved treatment options. Our clinical data and prior studies of AeroApoC3 have shown clear and dramatic reductions in triglycerides, so we are confident that AeroApoC3 is doing what it is designed to do. We are working to accrue patients in the Palisade study as quickly as possible since there is such high unmet need for these patients. In addition to starting our first Phase III study, we also completed enrollment in the Phase IIb ARCHES II study of aeroANG3, our other wholly-owned investigational cardiometabolic candidate for patients with mixed dyslipidemia. This study enrolled over 200 patients with LBH triglycerides and LDL cholesterol. Completion of ARCHES II is anticipated around the end of this year, and we intend to release top-line data in the first half of 2023. These data will inform the next phase of development, and potentially provide a path to another late-stage clinical study that we hope will be registrational. We also recently initiated the gateway study of AeroAng3 in patients with homozygous familial hypercholesterolemia, or HOFH. This study will evaluate the ability of AeroAng3 to reduce LDL cholesterol in patients with the most serious and rare form of familial hypercholesterolemia. We view the HOFH opportunity in a similar way to the FCS opportunity for AeroApoC3, where there may be a rapid path to approval in a narrow patient population with severe disease while we conduct larger clinical studies in higher prevalence indications. As I mentioned earlier, our investment in the new manufacturing facility is to support our growth into a commercial stage company. We think there are multiple opportunities to get there in the near to midterm, and we are preparing on all fronts. To that end, we appointed a new member of our board of directors. Vicki Vecchino is an accomplished commercial pharmaceutical executive with decades of experience building commercial organizations and launching new products across multiple therapeutic areas. She will have an important voice on the board and provide valuable input as our commercial strategy maps out. I also want to give a brief update on our later stage partner candidates. These are Olpasaran, targeting LP little a with Amgen, AeroAAT, also called TAC999 with Takeda, J&J3989, formerly AeroHBV for chronic hepatitis B infection with Janssen, and AeroHSD for treatment of NASH with GSK. Amgen has indicated publicly that Phase II clinical data for Olpaceran is expected around the middle of the year. They've also indicated that if the data are consistent with the positive data seen in Phase I, that they would move rapidly to start a Phase III study. We are very excited about this program and eager to see the phase two data. We believe that LBAT triglycerides, LP little a, LDL cholesterol, and possibly low levels or poorly functioning HDL are all contributors to the substantial remaining risk of cardiovascular disease, even in patients on maximal LDL lowering therapies. We have candidates addressing all of these. Our two wholly owned programs, AeroApoC3 and AeroAng3, and our partner program with Amgen may be able to address multiple lipids that contribute to this risk. We still need to conduct clinical studies to assess their efficacy and safety, but we have a high degree of confidence in these programs. Moving on to TAC 999, we are on schedule to collect the last 12-month biopsy from the last patient in the Sequoia study in June or July of this year. After the sample is taken, all clinical samples will be processed and analyzed, and biopsies will be prepped and read This process will likely take a few months, so we should have data available in the fall. Our intention would be to present those data in an appropriate forum. According to our agreement, Decatur will lead clinical developments and regulatory interactions after phase two. We will still be closely involved with the process and have had a very productive relationship with our colleagues at Decatur. We look forward to additional regulatory interactions this year and moving the program forward rapidly. J&J 3989, formerly Arrow HPV, is being investigated in multiple large Phase II studies that all include a follow-up phase. Together, these will include close to 1,000 patients on various combination therapies, and we would expect regular readouts for the foreseeable future as data come in. Public data thus far suggests that J&J 3989 is doing what it is designed to do and substantially reducing viral antigens. We are excited to see these data and are hopeful that they will point to a treatment that is desperately needed by the 300 million people thought to suffer from chronic hepatitis B infection worldwide. Our partnership with GSK for AeroHSD closed at the end of the first quarter this year. Since then, we have been working productively together and expect GSK to initiate a phase two study this year in patients with NASH. This represents a large unmet medical need. HSD is a genetically validated target. We believe we were the first to address this target clinically and our Phase I data were compelling in terms of knockdown, tolerability, and transaminase decreases in patients with suspected NASH. Complementing our mid- and later-stage pipeline, we were also active during the quarter expanding our early-stage clinical pipeline. We believe sustainable growth requires a diversified portfolio of candidates across the therapeutic areas, disease prevalence, and patient population size, and across stages of development. so it's critical that we both advance our later stage programs and also constantly expand our early stage pipeline. We must also remember that Arrowhead is really good at moving rapidly from idea to the clinic. We likely will not have the bandwidth to commercialize everything we produce, and we certainly do not intend to tap the brakes on early development. As such, some of those programs will be partnered to A, put them in the hands of companies that will move aggressively to get them to the patients who need them, and B, provide capital for us to commercialize our wholly owned assets. Developing important new medicines is an expensive business and we have the luxury of not being solely dependent upon the capital markets to fund this. We expect this year and every year for the foreseeable future to bring in significant capital from new and existing partnerships. I expect Arrowhead to commercialize a variety of important medicines and a targeted partnership strategy helps provide necessary capital for this while also providing potentially substantial long-term economics. We had three new clinical programs over the recent period. Arrow C3 for treatment of complement-mediated diseases, for which we initiated a Phase I-II clinical study, and our second and third pulmonary programs, Arrow RAGE and Arrow MUC5AC, for which we filed CTAs to initiate Phase I-II clinical studies. We'll talk more about Arrow RAGE and Arrow MUC5AC at our upcoming pulmonary R&D day, on May 26th. Arrowhead team members and two external key opinion leaders will talk about the treatment landscape for various mucloobstructive and inflammatory lung diseases and the role that RAGE and MUC5AC may play in addressing them. We will also discuss other advancements in the pulmonary platform and disclose the next pulmonary candidate we expect to bring to the clinic. During the quarter, we also presented interim results for a Phase 1b dose-finding study of ArrowHIF2, are investigational candidate for patients with clear cell renal cell carcinoma. The data presented provide initial proof of concept, I'm sorry, initial proof of target engagement based on reductions in HIF-2-alpha expression. We have been working on a HIF program for over a decade using different strategies and many different iterations of our delivery technologies. Our goals for that program were threefold. One, we wanted to develop a HIF-2-alpha targeted therapy because there is supportive evidence that it could have an effect for RCC patients and it had historically been undruggable with small molecules or monoclonal antibodies. Two, we wanted to validate that we could get functional delivery of siRNA to solid tumors, indicating that we may have a platform that can be applied to additional targets and cancer types. And three, we wanted to use the tumor delivery program as a way for us to learn critical lessons that could be applied to delivery systems targeted to various other extrahepatic tissues. We think we accomplished numbers two and three the therapeutic landscape has changed for goal number one the competitive environment is dramatically different today than it was just a few years ago with one small molecule hip2 alpha inhibitor fda approved and others in clinical development we have examined the data from our clinical study at this point based on the competitive environment we have decided not to continue further development of arrow hip2 this decision was made after significant deliberation and analysis and we would like to acknowledge and give our sincere thanks to the investigators, site staff, and of course patients who participated in our clinical study. However, as I mentioned, we did accomplish some important things with our first tumor targeted program. Probably the most critical piece that has wide ranging implications is that we learned more about how to optimize each individual component of the system to squeeze as much knockdown as possible out of each siRNA molecule. These lessons made it possible for us to develop the technology to get to various other extrahepatic tissues. We believe we are now much better at several things, including trigger design, optimizing chemical modifications, ligand design and selection, linker optimization, and design and use of PK-PD enhancing structures, as well as other things that can optimize target engagement. We also believe that we have a good start in our oncology platform. We saw clear target engagement, suggesting that we are able to deliver to solid tumors. In short, we are on the board. We are now using the lessons we learned from that study to further optimize the platform for use in other tumor types against new targets. We believe that RNAi can play a role in cancer treatment, and we are pushing in that direction. I want to highlight one more piece of corporate news. We recently announced that Arrowhead formed a joint venture called Vicerna Therapeutics with Vivo Capital to expand the reach of innovative medicines in greater China. Bevo provided initial funding of $60 million to Vicerna, which will have exclusive rights to develop and commercialize four of Arrowhead's investigational therapeutics for cardiometabolic diseases in mainland China, Hong Kong, Macau, and Taiwan. Arrowhead has a majority stake in Vicerna after accounting for shares reserved for the employee stock ownership plan and is further eligible to receive potential royalties on commercial sales. China is an increasingly important market for global pharmaceutical products. We believe to be successful in China, you are better off in a dedicated entity with its own management and development staff that understand and are solely focused on the intricacies of China's clinical, regulatory, and commercial environment. That is what we envision Vicerna becoming. We are looking for more than just a financial investor, and Vivo checked all the necessary boxes. Vivo has unique experience, expertise, and a local network to draw upon. that makes them a very valuable partner in this joint venture. We think this transaction allows us to maximize value and maximize the probability of success without losing focus on our core target markets for future commercialization. Really a win-win scenario and a transaction that we think over time has the potential to become substantially more valuable. We view this as another quarter where we executed well and achieved some key corporate goals. For a company our size with respect to headcount and market value, we have a uniquely broad and diverse set of assets. A key part of the Arrowhead DNA is a devotion to speed and precision, and a commitment to bring RNAi to intractable diseases. This prior period is a good example of that. With that overview, I'd now like to turn the call over to Dr. Javier San Martin. Javier?

Thank you, Chris, and good afternoon, everyone. I will provide updates on enrollment for the VISTA set of studies for ARO-H3 and the summit study for ARO-ApoC3 and give some forward guidance on anticipated timelines. I will start with the VISTA studies of ARO-H3, our investigational medicine designed to reduce production of angiopoietin-like protein-3 as a potential treatment for patients with dyslipidemia. There are currently two ARCHES studies, ARCHES-II in patients with mixed dyslipidemia and GATEWAY in patients with HOFH. ARCHES-II is a double-blind placebo-controlled Phase IIb study ARCHES II is a fully enrolled with 204 patients with triglycerides between 150 and 500 milligrams per deciliter, and non-HDL cholesterol greater than 100 milligrams per deciliter, or LDL cholesterol greater than 70 milligrams per deciliter. Being randomized in a three-to-one ratio to receive either subcutaneous injection of aero-H3 or placebo on day one and week 12, three dose levels of aero-H3 50 milligrams, 100 milligrams, and 200 milligrams are being evaluated against placebo. The duration of the study is approximately 42 weeks from screening to the week 36 end of study examination. After completing the week 36 visit, participant will be eligible to continue in an open-label extension period. Anticipated ARGES II will be completed around the end of 2022. and top-line data will be available to share in the first half of 2023. The next active study is GATEWAY, an open-level Phase II clinical study to evaluate the efficacy and safety of investigational ROH3 in up to 16 subjects with HOFH. Two dose levels of ROH3, 200 and 300 milligrams, will be evaluated in subjects with documented HOFH based on genotype or clinical criteria. and with fasting LDL cholesterol greater than 100 milligrams per deciliter and fasting triglycerides less than 300 milligrams per deciliter at screening. TAPCHES will receive a subcutaneous injection of AROH3 on day one and day 84 and may be eligible to participate in an optional open-label extension study. The primary objective of the gateway study is to evaluate the efficacy and safety of AROH3 in TAPCHES with HOFH And the primary input is the percent change in fasting-calculated LDL cholesterol from baseline to week 24. We just started opening clinical sites and enrolling gateway a few weeks ago, so we don't have a great visibility into how long it may take to accrue all 16 patients. Our goal is to have the study fully enrolled or at least have a meaningful amount of patients enrolled by the end of this year. Since this is an open-label study, we may be able to view results in somewhat real-time, so we intend to share data in 2023 when possible. Next, I will provide an update on the summit study of AeroApoC3, our investigation of the medicine targeting apolipoprotein C3 being studied in patients with various lipid disorders. There are three active studies. Just a two in patients with severe hyperthelicidemia, or SHTG, Neur in patients with mixed dyslipidemia, and Palisades in patients with FCS. CHASTA-2 is a double-blind placebo-controlled Phase IIb study in approximately 216 patients with triglycerides greater than 500 milligrams per deciliter. Three dose levels of AeroApoC3, 10 milligrams, 25 milligrams, and 50 milligrams, will be evaluated against placebo. The primary objective of the SHER-STAT-2 study is to evaluate the safety and efficacy of aeroeposy-3 and to select those in regimen for later stage clinical studies in this patient population. Moving on to the MIR study, which is a double-blind placebo-controlled Phase IIb study in approximately 320 patients with triglycerides between 150 and 500 milligrams per deciliter and known HDL cholesterol greater than 100 milligrams per deciliter. or LDL cholesterol greater than 70 milligrams per deciliter. In three cohorts, 10, 25, and 50 milligrams, each participant will receive subcutaneous injection on day one and week 12 for a total of two injections. And in one additional 50 milligram cohort, each participant will receive a subcutaneous injection on day one and week 24 for a total of two injections. The primary objective of the new year's study is to evaluate the safety and efficacy of aeroeposite 3 and to select the dose and dosing regimen for later stage clinical studies in patients with mixed dyslipidemia. TASTA-2 and MUIR are both approximately 50% enrolled, and we anticipate full enrollment in the fourth quarter of 2022. This would allow for study completions in 2023. The last study is the Summit Program in Palisades, a Phase III study in approximately 72 patients with FCS. Primary endpoint of palisades is the percentage from baseline at month 10 in fasting triglycerides. Additionally, secondary and exploratory endpoints include the change in other lead parameters, incidence of acute pancreatitis, and other measures. We're working hard to open clinical sites around the world to accrue the study as fast as possible. We originally anticipated recruiting a number of patients in Russia, Ukraine, and Belarus. However, due to the ongoing conflict, we have closed all clinical sites in the region. We're adding clinical sites in additional countries to maintain patient accrual. Our current goal is to have palisades fully enrolled in the middle of 2023, which would allow for study completion in 2024. I will now turn the call over to Dr. James Hamilton. James?