Financial Data and Key Metrics Changes - The net loss for fiscal year 2025 was $2 million, a significant improvement from a net loss of approximately $599 million in fiscal year 2024, resulting in a loss of $0.01 per share compared to a loss of $5 per share [32] - Revenue for fiscal year 2025 totaled $829 million, driven primarily by licensing and collaboration agreements, with $697 million from Sarepta Therapeutics [32][33] - Total operating expenses increased to approximately $731 million in fiscal year 2025 from $605 million in fiscal 2024, primarily due to higher R&D and SG&A costs [35] Business Line Data and Key Metrics Changes - The FDA approval of Redemplo marked a major milestone, being the first FDA-approved siRNA medicine for familial chylomicronemia syndrome (FCS) [7][8] - Redemplo achieved an unprecedented reduction in triglycerides by approximately 80% from baseline as early as one month, with 50% of patients at the 25-mg dose achieving triglyceride levels below 500 mg per deciliter [24] - The company has made progress with Zodasiran, initiating the Yosemite phase III clinical trial for homozygous familial hypercholesterolemia (HoFH) [11][12] Market Data and Key Metrics Changes - There are an estimated 6,500 people in the U.S. living with genetic or clinical FCS, and approximately 750,000 patients with persistent chylomicronemia at high risk for acute pancreatitis [10][25] - The One Redemplo pricing model is set at $60,000 annually, aimed at providing consistent pricing across current and future indications [25] Company Strategy and Development Direction - The company is focusing on the cardiometabolic space, with ongoing development programs for Zodasiran and ArrowDiamond PA, targeting large populations without proper treatment options [14][15] - Arrowhead aims to have 20 individual drug candidates in clinical trials by the end of 2025, with a balanced pipeline of wholly owned and partnered programs [41] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the commercial launch of Redemplo and the positive feedback received from healthcare professionals and patient societies [24][25] - The company anticipates that the commercial sales of Redemplo will not have a substantial impact on financial statements in fiscal year 2026, but believes its cash runway is sufficient to extend into fiscal year 2028 [39] Other Important Information - Arrowhead received a $200 million upfront payment from Novartis for a licensing agreement and is eligible for up to $2 billion in future milestone payments [18][37] - The company has expanded its clinical pipeline in CNS with AROMAPT, targeting tauopathies including Alzheimer's disease [15] Q&A Session Summary Question: Can you discuss the plan to show benefit in terms of acute pancreatitis for Plozasiran? - Management indicated that shots at three and four were powered for triglyceride reduction, with a reasonable chance to show a difference in acute pancreatitis, but emphasized that shots at five are specifically designed to demonstrate benefit in acute pancreatitis [45][46] Question: Can you provide more details on the upcoming data for obesity programs? - Management confirmed that initial data from the AROINHBE program will be shared in early January, with a focus on safety and biomarker data, while ARO-ALK7 will provide limited data focused on monotherapy safety [50][52] Question: What are the estimates on acute pancreatitis events accrual based on patient baseline characteristics? - Management noted that it is difficult to estimate the number of events due to the new criteria being used, but they expect to have a sufficient number of events based on the percentage of patients with a history of pancreatitis enrolled in the study [56] Question: Can you discuss the differentiation of the ArrowMapT program from J&J's failed anti-tau antibody? - Management highlighted that ArrowMapT targets intracellular tau, potentially reducing both intracellular and extracellular tau levels, unlike J&J's approach which primarily targets extracellular tau [62] Question: What is the visibility on launching a CBOT study? - Management indicated that they expect to have a clearer idea by summer regarding the data from ongoing studies, which will inform the timeline for launching pivotal studies [65]

Financial Data and Key Metrics Changes - The net loss for fiscal year 2025 was $2 million, a significant improvement from a net loss of approximately $599 million in fiscal year 2024, resulting in a loss of $0.01 per share compared to a loss of $5 per share [32] - Revenue for fiscal year 2025 totaled $829 million, driven primarily by licensing and collaboration agreements, with $697 million from Sarepta Therapeutics [32][33] - Total operating expenses for fiscal year 2025 were approximately $731 million, an increase from $605 million in fiscal 2024, primarily due to higher R&D and SG&A costs [33][34] - Cash and investments totaled $919 million as of September 30, 2025, up from $681 million a year earlier, reflecting strong cash flow from licensing agreements [35][36] Business Line Data and Key Metrics Changes - The FDA approved Redemplo, Arrowhead's first FDA-approved medicine, marking a major milestone as it transitions into the commercial stage [6][7] - Redemplo is indicated for reducing triglycerides in adults with familial chylomicronemia syndrome (FCS) and can be self-administered at home [19][20] - The One Redemplo pricing model is set at $60,000 annually, aimed at providing consistent pricing across indications [11][25] Market Data and Key Metrics Changes - There are an estimated 6,500 people in the U.S. living with genetic or clinical FCS, with a prescriber base comprising specialists such as lipidologists and endocrinologists [25] - The broader patient population at risk of acute pancreatitis includes approximately 750,000 patients with persistent chylomicronemia [10] Company Strategy and Development Direction - The company is focusing on the cardiometabolic space, with ongoing clinical trials for Zodasiran and ArrowDiamond PA, targeting conditions like homozygous familial hypercholesterolemia and atherosclerotic cardiovascular disease [12][13] - Arrowhead aims to have 20 individual drug candidates in clinical trials by the end of 2025, with a balanced pipeline of wholly owned and partnered programs [39] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the commercial launch of Redemplo and the encouraging feedback from the FCS community [39] - The company does not anticipate substantial financial impact from Redemplo sales in fiscal year 2026 but believes its cash runway is sufficient to support operations into fiscal year 2028 [38] Other Important Information - Arrowhead received a $200 million upfront payment from Novartis for a licensing agreement and is eligible for up to $2 billion in future milestone payments [36][37] - The company has made significant progress in business development, including a $200 million milestone payment from Sarepta for ARO-DM1 [17][38] Q&A Session Summary Question: What is the plan to show benefit in terms of acute pancreatitis for Plozasiran? - Management indicated that while shots at three and four were powered for triglyceride reduction, there is reasonable power to see a difference in acute pancreatitis, with a specific design for SHASTA-5 to demonstrate benefit [42][44][45] Question: Can you provide details on the upcoming data for obesity programs? - Management confirmed that initial data from the ARO-INHBE program will be shared in early January, with a focus on safety and biomarker data [48][50] Question: What are the estimates on acute pancreatitis events accrual based on patient baseline characteristics? - Management noted that it is challenging to predict due to the adoption of modified Atlanta criteria for adjudication, but they expect a sufficient number of events based on patient history [53][54] Question: Can you discuss the differentiation of ArrowMapT from J&J's failed anti-tau antibody? - Management highlighted that ArrowMapT targets intracellular tau, potentially reducing both intracellular and extracellular tau levels, unlike J&J's approach [57][59] Question: What is the visibility on launching a CBOT study? - Management stated that they expect to have a clearer idea by summer 2026 based on data from ongoing studies, with plans to move into pivotal studies if results are favorable [62][63]

Drug Development and Clinical Trials - The Company has 18 drug candidates in clinical trials, ranging from Phase 1 to Phase 3, with a robust discovery pipeline capable of generating multiple new clinical candidates each year[19] - REDEMPLO (plozasiran) was approved by the FDA in 2025 to reduce triglycerides in adults with Familial Chylomicronemia Syndrome (FCS), marking the Company's first commercial launch[20] - The Company plans to file a supplemental NDA for severe hypertriglyceridemia (sHTG) in 2026, pending successful completion of Phase 3 studies[20] - ARO-DIMER-PA is a dual functional RNAi molecule targeting PCSK9 and APOC3, representing a significant advancement in RNAi therapeutics[48] - The Company is investigating ARO-MAPT, designed to silence the MAPT gene, in a Phase 1/2a clinical trial for Alzheimer's and tauopathies[57] - ARO-CFB is being developed as a potential treatment for complement-mediated kidney diseases, currently in a Phase 1/2a clinical trial[61] - GSK is conducting Phase 2b clinical trials for GSK-4532990 targeting metabolic-dysfunction associated steatohepatitis (MASH) and alcohol-related liver disease (ALD)[65] - GSK received a worldwide exclusive license for daplusiran/tomligisiran (GSK5637608) to develop a potential therapy for chronic hepatitis B virus infection, with a Phase 2 study currently being initiated[66] - Takeda and the Company co-develop the fazirsiran program for liver disease associated with alpha-1 antitrypsin deficiency, with a 50/50 profit-sharing structure in the U.S.[67] - Fazirsiran aims to reduce the production of the mutant Z-AAT protein to prevent liver injury and fibrosis in patients with alpha-1 antitrypsin deficiency[70] - Amgen is responsible for the clinical development of olpasiran, designed to reduce elevated lipoprotein(a), a risk factor for atherosclerotic cardiovascular disease[73] Regulatory and Compliance - The FDA requires a user fee of approximately $4.682 million for NDA submissions requiring clinical data for fiscal year 2026[106] - The FDA's review process for NDAs typically aims for completion within ten months, with priority reviews targeted at six months[108] - The Company must comply with cGMP requirements to ensure consistent production of its products before the FDA approves an NDA[109] - The FDA may require a REMS plan to mitigate serious risks associated with a drug, which can affect market potential and profitability[110] - The FDA may impose conditions on approved products, including post-approval studies and distribution restrictions, which can materially affect market dynamics[113] - The FDA may not approve any other application to market the same drug for the same indication for seven years, except in very limited circumstances[116] - The FDA's interpretation of orphan drug exclusivity may change, potentially limiting the drugs that can receive such exclusivity[117] - Fast Track Designation allows for priority review and rolling review for drugs addressing serious conditions with unmet medical needs[118] - The FDA may approve a drug under the accelerated approval program if it provides a meaningful advantage over existing therapies and demonstrates an effect on a surrogate endpoint[119] - The Breakthrough Therapy designation provides more intensive guidance and expedited review for drugs showing substantial improvement over existing therapies[120] - Post-approval requirements include ongoing regulation by the FDA, including recordkeeping and reporting of adverse experiences[121] - Drug manufacturers must register with the FDA and are subject to periodic inspections to ensure compliance with cGMP requirements[122] - The FDA may withdraw approval if compliance with regulatory requirements is not maintained or if new problems are discovered post-market[123] Intellectual Property and Licensing - The Company controls approximately 643 issued patents and has around 833 pending patent applications worldwide, covering various RNAi technologies[85] - The Company may need to obtain additional patent licenses prior to commercialization of its candidates due to the complex patent landscape in RNAi and drug delivery[89] - The Company acquired RNAi assets and rights from Novartis, including patents related to RNAi therapeutics and delivery technologies[90] - The acquisition from Roche provided the Company with licenses to patents related to modifications of double-stranded oligonucleotides, enhancing its operational freedom in RNAi-trigger formats[91][92] - The Company holds a worldwide, royalty-bearing, exclusive license under the Alnylam-Novartis License to research, develop, and commercialize 30 undisclosed gene targets[90] Market Exclusivity and Orphan Drug Designation - Orphan drug designation can provide the Company with incentives such as grant funding and tax advantages for drugs intended to treat rare diseases[114] - The company is subject to a 10-year market exclusivity for orphan medicinal products, which can be reduced to six years if criteria are not met[165] - Orphan drug designation provides up to ten years of market exclusivity in the EU, contingent on maintaining the designation at the time of marketing authorization review[163] Manufacturing and Workforce - The Company expanded its footprint with a new manufacturing and laboratory facility in Verona, Wisconsin during Q1 fiscal 2025[208] - The new state-of-the-art GMP manufacturing facility in Verona includes over 251,000 total square feet of laboratories and office space[211] - As of September 30, 2025, the Company employed 711 full-time employees across four facilities in the U.S.[212] - The Company continues to expand its workforce to increase in-house manufacturing capacity and enhance clinical and preclinical research expertise[213] - The Company offers a total compensation package targeting the 50 to 75 percentile of the market, including base salary, cash bonuses, and equity compensation[214] - The Company supports employee development through individualized plans, mentoring, and tuition reimbursement[214] - The Company is committed to fostering an inclusive environment with ongoing programs for awareness and engagement[215] Data Privacy and Security - The company must comply with various data privacy and security laws, including HIPAA and state privacy laws, which impose significant obligations regarding personal information[185] - Failure to comply with data privacy laws can result in substantial civil and criminal penalties, posing financial and reputational risks to the company[188] - The GDPR and UK GDPR impose fines of up to €20 million or 4% of annual global revenues for noncompliance, whichever is greater[191] - The complexity of data protection regulations in the EEA is heightened by varying enforcement and additional national regulations[191] - The transfer of personal data outside the EEA requires appropriate safeguards, such as standard contractual clauses[193] Pricing and Reimbursement - The pricing and reimbursement environment in the EU allows member states to control prices and reimbursement levels, which may affect market access for the company's products[177] - Health technology assessments (HTA) are increasingly influencing pricing and reimbursement decisions in EU member states, focusing on clinical efficacy, safety, and cost-effectiveness[179] - The company may be required to conduct cost-effectiveness studies to obtain favorable pricing and reimbursement conditions in certain EU member states[182] - Orphan pharmaceutical products may be exempted from providing certain clinical and economic data for pricing/reimbursement approval in some EU member states[183] Regulatory Changes in the EU - The UK government enacted the Medicines and Medical Devices Act 2021 to update regulatory frameworks for human medicines and clinical trials, ensuring public health is safeguarded[141] - The centralized procedure for Marketing Authorization (MA) in the EU has a standard evaluation timeframe of 210 days, which can be extended due to additional information requests[152] - New Chemical Entities (NCE) approved in the EU qualify for eight years of data exclusivity and ten years of marketing exclusivity, extendable to eleven years under certain conditions[157] - The European Medicines Agency (EMA) provides scientific advice for drug development, with fees significantly reduced for orphan medicines[149] - The Medical Devices (Amendment) (Great Britain) Regulations 2023 allow CE marked devices to be sold in the UK until 2028 or 2030, depending on the device type[144] - The Medicines and Healthcare products Regulatory Agency (MHRA) plans to implement new 'Pre-Market Regulations' in 2026, extending the sunset period for key EU-derived regulations[144] - The EU Clinical Trials Regulation (CTR) became applicable on January 31, 2022, streamlining the approval process for clinical trials across member states[145] - The current proposal for reforming European pharmaceutical legislation includes shortening data exclusivity from eight to six years, with incentives for developing new antibiotics[161]

Financial Performance - Arrowhead Pharmaceuticals reported a revenue of $829.448 million for the fiscal year 2025, a significant increase from $3.551 million in 2024[10] - The company achieved an operating income of $98.346 million in 2025, compared to an operating loss of $601.080 million in 2024[10] - Arrowhead's net income attributable to the company was a loss of $1.631 million in 2025, an improvement from a loss of $599.493 million in the previous year[10] - The company has $919.366 million in total cash resources as of September 30, 2025, compared to $680.961 million in 2024[10] - Arrowhead's total assets increased to $1.385 billion in 2025, up from $1.140 billion in 2024[10] Regulatory Approvals and Clinical Trials - The FDA approved REDEMPLO (plozasiran), the first FDA-approved siRNA medicine for familial chylomicronemia syndrome (FCS), which can reduce triglycerides by 80% from baseline[6][11] - The company filed for regulatory clearance to initiate Phase 1/2a clinical trials for ARO-DIMER-PA and ARO-MAPT, targeting atherosclerotic cardiovascular disease and tauopathies, respectively[7] Partnerships and Licensing Agreements - Arrowhead received a $200 million upfront payment from Novartis as part of a global licensing agreement for ARO-SNCA, with potential milestone payments of up to $2 billion[7] - Arrowhead earned $300 million in milestone payments from Sarepta Therapeutics related to the ARO-DM1 clinical study[7] - The company signed an asset purchase agreement with Sanofi, receiving an upfront payment of $130 million and potential milestone payments of up to $265 million for plozasiran in Greater China[8]

Summary of Arrowhead Pharmaceuticals Conference Call Company Overview - **Company**: Arrowhead Pharmaceuticals (NasdaqGS:ARWR) - **Event**: Conference at TD Cowen's 2025 Treatment Advances in Obesity Summit - **Date**: November 24, 2025 Key Points Recent Progress and Upcoming Expectations - Arrowhead recently received the first approval for Redemplo in FCS (Familial Chylomicronemia Syndrome) and plans to provide updates on its launch progress in the upcoming quarterly call [2][28] - The company is set to release data from its INHBE and ALK-7 programs in early January 2026, following the holiday season [2][5] - Initiation of the dimer phase one study for ApoC3 PCSK9 is expected early next year [3] Obesity Treatment Focus - Arrowhead identifies a significant unmet need in obesity treatment, particularly in achieving greater fat mass loss while sparing lean tissue [5] - There is potential for therapeutics that induce moderate weight loss (7-10%) with better tolerability profiles compared to GLP-1s [5][6] - The company is exploring gene targets in adipocytes and hepatocytes to silence genes related to fat storage and metabolism [6] INHBE Program Insights - INHBE encodes Activin E, a protein involved in fat storage regulation, primarily expressed in the liver [8] - Dysregulation of Activin E signaling can lead to increased fat storage, particularly in individuals with excessive caloric intake or type 2 diabetes [9] - Preclinical studies in diet-induced obesity mouse models showed a 20% reduction in weight gain with INHBE siRNA treatment compared to controls [10] - Combination studies with GLP-1s demonstrated additive weight loss effects while preserving lean mass [11] Clinical Trial Updates - The ongoing phase one study includes single and multiple ascending dose cohorts in healthy obese volunteers and type 2 diabetic patients [13][14] - The study is nearly fully enrolled, with a focus on safety and biomarker knockdown, particularly measuring Activin E levels [15] - Initial data release is expected in early 2026, with a critical mass of data needed to make decisions on moving forward with candidates [27] ALK-7 Program Comparison - ALK-7 targets a receptor on adipocytes, utilizing a novel delivery platform, while INHBE targets the liver signaling pathway [20][21] - Preclinical data for ALK-7 showed a 40% reduction in fat mass in treated animals, suggesting it may be a more potent approach than INHBE [21][22] - Both programs are designed to address obesity but through different mechanisms, with ongoing studies to determine their relative efficacy [23] Redemplo Launch Expectations - Initial launch expectations for Redemplo are positive, with significant interest from investigators and potential patients [28] - The company is cautious about pricing strategies and will provide updates in the upcoming earnings call [28] Future Outlook - Arrowhead anticipates a robust data release in early 2026, which will inform decisions on the progression of its obesity programs and potential partnerships [27] - The company is also monitoring the competitive landscape, particularly in relation to other siRNA approaches targeting similar pathways [18] Additional Considerations - The company is focused on differentiating its products based on efficacy, tolerability, and the quality of weight loss achieved [16] - Ongoing studies will help clarify the impact of treatments on liver fat content and overall metabolic health [30][31]

Summary of Arrowhead Pharmaceuticals Conference Call Company Overview - Arrowhead Pharmaceuticals is an RNA interference (RNAi) company focused on developing therapies across various disease areas rather than concentrating on a single disease type [4][6] - The company has five clinical programs targeting different cell types, with a total of 20 drug candidates in clinical studies by the end of the year [4][6] Core Products and Market Opportunities - **Redemplo (Plozasiran)**: Recently approved by the FDA for treating Familial Chylomicronemia Syndrome (FCS) patients, aiming to lower triglycerides and reduce pancreatitis risk [6][10] - **Severe Hypertriglyceridemia (SHTG)**: The company plans to expand into this market, which includes approximately 3.5 million people with triglycerides above 500, focusing on a high-risk population of 750,000 to 1 million individuals with triglycerides above 800 [6][7][32] - **Pricing Strategy**: Redemplo is priced at $60,000 annually, which is positioned as a pancreatitis drug rather than a standard cardiovascular drug, aiming to justify its pricing to payers and providers [8][10][11] Competitive Landscape - Arrowhead's Redemplo is compared to Ionis's drug, which is priced lower but has shown less efficacy in triglyceride reduction [14][15] - The company emphasizes the importance of having multiple players in the market to build awareness and treatment options for SHTG [16] Clinical Trials and Data Expectations - Ongoing phase III studies (Shasta III, Shasta IV, and MIR3) are expected to provide top-line data in mid-2026, with a focus on triglyceride reduction and pancreatitis risk [17][19] - The company is harmonizing its pancreatitis event adjudication criteria with Ionis to ensure consistency in data reporting [26][28] Safety and Efficacy - Arrowhead reports a clean safety profile for Redemplo, with no significant adverse effects observed in clinical trials [29][30] - The company is monitoring potential increases in liver fat, which have been a concern for competitors [30] Future Catalysts - Key upcoming events include the launch of Redemplo, early data from the Alzheimer's drug ARO-MAPT, and results from the dimer targeting PCSK9 and ApoC3 [50][51] - The company anticipates significant developments in 2026, including potential market expansion and new data releases [50][51] Additional Programs - Arrowhead is also developing obesity treatments (ARO-INHBE and ARO-ALK7) and has ongoing collaborations with Sarepta for DUX4 and DM1 programs, with milestones expected soon [44][48] Conclusion - Arrowhead Pharmaceuticals is positioned to make significant strides in the RNAi space with its innovative therapies targeting high-risk populations, while also navigating competitive pricing and market access challenges. The upcoming data releases and product launches are critical for the company's growth trajectory.

Core Viewpoint - Arrowhead Pharmaceuticals has received FDA approval for REDEMPLO, a treatment aimed at reducing triglycerides in adults with familial chylomicronemia syndrome (FCS) [2]. Group 1: FDA Approval - The FDA approval of REDEMPLO is a significant milestone for Arrowhead Pharmaceuticals, as it addresses a critical need for patients suffering from FCS [2]. Group 2: Financial and Investor Relations - Vince Anzalone, Vice President of Finance and Investor Relations, is leading the discussion on the implications of this approval for the company's future [1].

Group 1 - The article does not provide any relevant content regarding company or industry insights [1]

Core Insights - Arrowhead Pharmaceuticals, Inc. achieved a significant milestone with the approval of their lead drug candidate REDEMPLO™ (formerly known as Plozasiran) on November 18th [1] Company Summary - REDEMPLO™ is positioned as a transformative drug for Arrowhead Pharmaceuticals, marking a pivotal moment in the company's development and potential market impact [1] Industry Context - The approval of REDEMPLO™ reflects ongoing advancements in the pharmaceutical industry, particularly in the area of innovative drug development [1]

Core Insights - Arrowhead Pharmaceuticals, Inc. (ARWR) achieved a significant milestone with the approval of their lead drug candidate REDEMPLO™ (formerly known as Plozasiran) on November 18th [1] Company Summary - REDEMPLO™ represents a transformational advancement for Arrowhead Pharmaceuticals, marking a pivotal moment in the company's development pipeline [1]